amphetamine sulfate

　

WordNet

1. a sulfate derivative of amphetamine that is used as a stimulant for the central nervous system (同)amphetamine sulphate
2. convert into a sulfate
3. a salt or ester of sulphuric acid (同)sulphate
4. a central nervous system stimulant that increases energy and decreases appetite; used to treat narcolepsy and some forms of depression (同)pep_pill, upper, speed

PrepTutorEJDIC

1. アンフェタミン(中枢神経刺激済)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/02 19:55:19」(JST)

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This article is about mixtures of levoamphetamine and dextroamphetamine. For other uses, see Amphetamine (disambiguation).

Amfetamine (INN)

Systematic (IUPAC) name
(RS)-1-phenylpropan-2-amine
Clinical data
Pronunciation	i/æmˈfɛtəmiːn/
AHFS/Drugs.com	entry
Licence data	US FDA:link
Pregnancy category	US: C (Risk not ruled out)
Legal status	AU: S8 (Controlled) CA: Schedule I DE: Anlage III NZ: Class B UK: Class B US: Schedule II UN: Psychotropic Schedule II
Dependence liability	Physical: none Psychological: moderate
Addiction liability	Moderate
Routes of administration	Medical: oral, nasal inhalation Recreational: oral, nasal inhalation, insufflation, rectal, intravenous
Pharmacokinetic data
Bioavailability	Rectal 95–100%; Oral 75–100%
Protein binding	15–40%
Metabolism	Amphetamine only: CYP2D6, DBH, FMO3
Metabolites	4-hydroxyamphetamine, 4-hydroxynorephedrine, 4-hydroxyphenylacetone, benzoic acid, hippuric acid, norephedrine, phenylacetone
Onset of action	IR dosing: Rapid XR dosing: 1.5–2 hours
Biological half-life	D-amph:9–11 hours L-amph:11–14 hours pH-dependent: 8–31 hours
Duration of action	IR dosing: 3–7 hours XR dosing: 12 hours
Excretion	Primarily renal; pH-dependent range: 1–75%
Identifiers
CAS Number	300-62-9 Y
ATC code	N06BA01
PubChem	CID: 3007
IUPHAR/BPS	4804
DrugBank	DB00182 Y
ChemSpider	13852819 Y
UNII	CK833KGX7E Y
KEGG	D07445 Y
ChEBI	CHEBI:2679 Y
ChEMBL	CHEMBL405 Y
NIAID ChemDB	018564
Synonyms	α-methylphenethylamine
PDB ligand ID	FRD (PDBe, RCSB PDB)
Chemical data
Formula	C9H13N
Molecular mass	135.20622 g/mol
SMILES NC(CC1=CC=CC=C1)C
InChI InChI=1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3 Y Key:KWTSXDURSIMDCE-UHFFFAOYSA-N Y
Physical data
Density	0.9±0.1 g/cm3
Melting point	11.3 °C (52.3 °F) (predicted)
Boiling point	203 °C (397 °F) at 760 mm Hg
Y (what is this?)  (verify)

Amphetamine (contracted from alpha‑methylphenethylamine) is a potent central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. Amphetamine was discovered in 1887 and exists as two enantiomers: levoamphetamine and dextroamphetamine. Amphetamine properly refers to a specific chemical, the racemic free base, which is equal parts of the two enantiomers, levoamphetamine and dextroamphetamine, in their pure amine forms. However, the term is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion, depression, and obesity. Amphetamine is also used as a performance and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. It is a prescription medication in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to the significant health risks associated with recreational use.

The first pharmaceutical amphetamine was Benzedrine, a brand of inhalers used to treat a variety of conditions. Currently, pharmaceutical amphetamine is prescribed as racemic amphetamine, Adderall, dextroamphetamine, or the inactive prodrug lisdexamfetamine. Amphetamine, through activation of a trace amine receptor, increases biogenic amine and excitatory neurotransmitter activity in the brain, with its most pronounced effects targeting the catecholamine neurotransmitters norepinephrine and dopamine. At therapeutic doses, this causes emotional and cognitive effects such as euphoria, change in libido, increased wakefulness, and improved cognitive control. It induces physical effects such as decreased reaction time, fatigue resistance, and increased muscle strength.

Much larger doses of amphetamine may impair cognitive function and induce rapid muscle breakdown. Drug addiction is a serious risk with large recreational doses, but rarely arises from medical use. Very high doses can result in psychosis (e.g., delusions and paranoia) which rarely occurs at therapeutic doses even during long-term use. Recreational doses are generally much larger than prescribed therapeutic doses and carry a far greater risk of serious side effects.

Amphetamine belongs to the phenethylamine class. It is also the parent compound of its own structural class, the substituted amphetamines, which includes prominent substances such as bupropion, cathinone, MDMA (ecstasy), and methamphetamine. As a member of the phenethylamine class, amphetamine is also chemically related to the naturally occurring trace amine neuromodulators, specifically phenethylamine and N-methylphenethylamine, both of which are produced within the human body. Phenethylamine is the parent compound of amphetamine, while N-methylphenethylamine is a constitutional isomer that differs only in the placement of the methyl group.

Uses

Medical

Amphetamine is used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy (a sleep disorder), and obesity, and is sometimes prescribed off-label for its past medical indications, such as depression and nasal congestion. Long-term amphetamine exposure in some animal species is known to produce abnormal dopamine system development or nerve damage, but, in humans with ADHD, pharmaceutical amphetamines appear to improve brain development and nerve growth. Reviews of magnetic resonance imaging (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus of the basal ganglia.

Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD. Controlled trials spanning two years have demonstrated treatment effectiveness and safety. One review highlighted a nine-month randomized controlled trial in children with ADHD that found an average increase of 4.5 IQ points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity.

Current models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems; these functional impairments involve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the locus coeruleus and prefrontal cortex. Psychostimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems. Approximately 80% of those who use these stimulants see improvements in ADHD symptoms. Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans. The Cochrane Collaboration's review on the treatment of adult ADHD with pharmaceutical amphetamines stated that while these drugs improve short-term symptoms, they have higher discontinuation rates than non-stimulant medications due to their adverse side effects. A Cochrane Collaboration review on the treatment of ADHD in children with tic disorders such as Tourette syndrome indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine could exacerbate tics in some individuals.

Enhancing performance

In 2015, a systematic review and a meta-analysis of high quality clinical trials found that, when used at low (therapeutic) doses, amphetamine produces modest, unambiguous improvements in cognition, including working memory, episodic memory, and inhibitory control, in normal healthy adults; the cognition-enhancing effects of amphetamine are known to occur through its indirect activation of both dopamine receptor D₁ and adrenoceptor A₂ in the prefrontal cortex. Therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals. Amphetamine and other ADHD stimulants also improve task saliency (motivation to perform a task) and increase arousal (wakefulness), in turn promoting goal-directed behavior. Stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid. Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily used for performance enhancement rather than as recreational drugs. However, high amphetamine doses that are above the therapeutic range can interfere with working memory and other aspects of cognitive control.

Amphetamine is used by some athletes for its psychological and performance-enhancing effects, such as increased stamina and alertness; however, its use is prohibited at sporting events regulated by collegiate, national, and international anti-doping agencies. In healthy people at oral therapeutic doses, amphetamine has been shown to increase physical strength, acceleration, stamina, and endurance, while reducing reaction time. Amphetamine improves stamina, endurance, and reaction time primarily through reuptake inhibition and effluxion of dopamine in the central nervous system. At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance; however, at much higher doses, amphetamine can induce effects that severely impair performance, such as rapid muscle breakdown and elevated body temperature.

Contraindications

See also: Amphetamine § Interactions

According to the International Programme on Chemical Safety (IPCS) and United States Food and Drug Administration (USFDA), amphetamine is contraindicated in people with a history of drug abuse, heart disease, severe agitation, or severe anxiety. It is also contraindicated in people currently experiencing arteriosclerosis (hardening of the arteries), glaucoma (increased eye pressure), hyperthyroidism (excessive production of thyroid hormone), or moderate to severe hypertension. People who have experienced allergic reactions to other stimulants in the past or who are taking monoamine oxidase inhibitors (MAOIs) are advised not to take amphetamine, although safe concurrent use of amphetamine and monoamine oxidase inhibitors has been documented. These agencies also state that anyone with anorexia nervosa, bipolar disorder, depression, hypertension, liver or kidney problems, mania, psychosis, Raynaud's phenomenon, seizures, thyroid problems, tics, or Tourette syndrome should monitor their symptoms while taking amphetamine. Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in the fetus or newborns (i.e., it is not a human teratogen), but amphetamine abuse does pose risks to the fetus. Amphetamine has also been shown to pass into breast milk, so the IPCS and USFDA advise mothers to avoid breastfeeding when using it. Due to the potential for reversible growth impairments, the USFDA advises monitoring the height and weight of children and adolescents prescribed an amphetamine pharmaceutical.

Side effects

The side effects of amphetamine are varied, and the amount of amphetamine used is the primary factor in determining the likelihood and severity of side effects. Amphetamine products such as Adderall, Dexedrine, and their generic equivalents are currently approved by the USFDA for long-term therapeutic use. Recreational use of amphetamine generally involves much larger doses, which have a greater risk of serious side effects than dosages used for therapeutic reasons.

Physical

At normal therapeutic doses, the physical side effects of amphetamine vary widely by age and from person to person. Cardiovascular side effects can include hypertension or hypotension from a vasovagal response, Raynaud's phenomenon (reduced blood flow to extremities), and tachycardia (increased heart rate). Sexual side effects in males may include erectile dysfunction, frequent erections, or prolonged erections. Abdominal side effects may include abdominal pain, loss of appetite, nausea, and weight loss. Other potential side effects include acne, blurred vision, dry mouth, excessive grinding of the teeth, nosebleed, profuse sweating, rhinitis medicamentosa (drug-induced nasal congestion), reduced seizure threshold, and tics (a type of movement disorder). Dangerous physical side effects are rare at typical pharmaceutical doses.

Amphetamine stimulates the medullary respiratory centers, producing faster and deeper breaths. In a normal person at therapeutic doses, this effect is usually not noticeable, but when respiration is already compromised, it may be evident. Amphetamine also induces contraction in the urinary bladder sphincter, the muscle which controls urination, which can result in difficulty urinating. This effect can be useful in treating bed wetting and loss of bladder control. The effects of amphetamine on the gastrointestinal tract are unpredictable. If intestinal activity is high, amphetamine may reduce gastrointestinal motility (the rate at which content moves through the digestive system); however, amphetamine may increase motility when the smooth muscle of the tract is relaxed. Amphetamine also has a slight analgesic effect and can enhance the pain relieving effects of opioids.

USFDA-commissioned studies from 2011 indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events (sudden death, heart attack, and stroke) and the medical use of amphetamine or other ADHD stimulants.

Psychological

Common psychological effects of therapeutic doses can include increased alertness, apprehension, concentration, decreased sense of fatigue, mood swings (elated mood followed by mildly depressed mood), increased initiative, insomnia or wakefulness, self-confidence, and sociability. Less common side effects include anxiety, change in libido, grandiosity, irritability, repetitive or obsessive behaviors, and restlessness; these effects depend on the user's personality and current mental state. Amphetamine psychosis (e.g., delusions and paranoia) can occur in heavy users. Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy. According to the USFDA, "there is no systematic evidence" that stimulants produce aggressive behavior or hostility.

Amphetamine has also been shown to produce a conditioned place preference in humans taking therapeutic doses, meaning that individuals acquire a preference for spending time in places where they have previously used amphetamine.

Overdose

An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care. The severity of overdose symptoms increases with dosage and decreases with drug tolerance to amphetamine. Tolerant individuals have been known to take as much as 5 grams of amphetamine in a day, which is roughly 100 times the maximum daily therapeutic dose. Symptoms of a moderate and extremely large overdose are listed below; fatal amphetamine poisoning usually also involves convulsions and coma. In 2013, overdose on amphetamine, methamphetamine, and other compounds implicated in an "amphetamine use disorder" resulted in an estimated 3,788 deaths worldwide (3,425–4,145 deaths, 95% confidence).

Pathological overactivation of the mesolimbic pathway, a dopamine pathway that connects the ventral tegmental area to the nucleus accumbens, plays a central role in amphetamine addiction. Individuals who frequently overdose on amphetamine during recreational use have a high risk of developing an amphetamine addiction, since repeated overdoses gradually increase the level of accumbal ΔFosB, a "molecular switch" and "master control protein" for addiction. Once nucleus accumbens ΔFosB is sufficiently overexpressed, it begins to increase the severity of addictive behavior (i.e., compulsive drug-seeking) with further increases in its expression. While there are currently no effective drugs for treating amphetamine addiction, regularly engaging in sustained aerobic exercise appears to reduce the risk of developing such an addiction. Sustained aerobic exercise on a regular basis also appears to be an effective treatment for amphetamine addiction; exercise therapy improves clinical treatment outcomes and may be used as a combination therapy with cognitive behavioral therapy, which is currently the best clinical treatment available.

Overdose symptoms by system

System	Minor or moderate overdose	Severe overdose
Cardiovascular	Abnormal heartbeat High or low blood pressure	Cardiogenic shock (heart not pumping enough blood) Cerebral hemorrhage (bleeding in the brain) Circulatory collapse (partial or complete failure of the circulatory system)
Central nervous system	Confusion Abnormally fast reflexes Severe agitation Tremor (involuntary muscle twitching)	Amphetamine psychosis (e.g., delusions and paranoia) Compulsive and repetitive movement Serotonin syndrome (excessive serotonergic nerve activity) Sympathomimetic toxidrome (excessive adrenergic nerve activity)
Musculoskeletal	Muscle pain	Rhabdomyolysis (rapid muscle breakdown)
Respiratory	Rapid breathing	Pulmonary edema (fluid accumulation in the lungs) Pulmonary hypertension (high blood pressure in the arteries of the lung) Respiratory alkalosis (reduced blood CO2)
Urinary	Painful urination Urinary retention (inability to urinate)	No urine production Kidney failure
Other	Elevated body temperature	Elevated or low blood potassium Hyperpyrexia (extremely elevated body temperature) Metabolic acidosis (excessively acidic bodily fluids)

Addiction

Addiction and dependence glossary
• addiction – a state characterized by compulsive engagement in rewarding stimuli despite adverse consequences
• reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them
• rewarding stimuli – stimuli that the brain interprets as intrinsically positive or as something to be approached
• addictive drug – a drug that is both rewarding and reinforcing
• addictive behavior – a behavior that is both rewarding and reinforcing
• sensitization – an amplified response to a stimulus resulting from repeated exposure to it
• tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose
• drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose
• dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
• physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)
• psychological dependence – dependence that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia)

Signaling cascade in the nucleus accumbens that results in amphetamine addiction

Note: colored text contains article links.

Nuclear pore

Nuclear membrane

Plasma membrane

Ca_v1.2

NMDAR

AMPAR

DRD1

DRD5

DRD2

DRD3

DRD4

G_s

G_i/o

cAMP

cAMP

PKA

CaM

CaMKII

DARPP-32

PP1

PP2B

CREB

ΔFosB

JunD

c-Fos

SIRT1

HDAC1

This diagram depicts the signaling events in the brain's reward center that are induced by chronic high-dose exposure to psychostimulants that increase the concentration of synaptic dopamine, like amphetamine, methamphetamine, and phenethylamine. Following presynaptic dopamine and glutamate co-release by such psychostimulants, postsynaptic receptors for these neurotransmitters trigger internal signaling events through a cAMP pathway and calcium-dependent pathway that ultimately result in increased CREB phosphorylation. Phosphorylated CREB increases levels of ΔFosB, which in turn represses the c-fos gene with the help of corepressors; c-fos repression acts as a molecular switch that enables the accumulation of ΔFosB in the neuron. A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for one or two months, slowly accumulates following repeated exposure to stimulants through this process. ΔFosB functions as "one of the master control proteins" that produces addiction-related structural changes in the brain, and upon sufficient accumulation, with the help of its downstream targets (e.g., nuclear factor kappa B), it induces an addictive state. 

Addiction is a serious risk with heavy recreational amphetamine use but is unlikely to arise from typical medical use at therapeutic doses. Drug tolerance develops rapidly in amphetamine abuse (i.e., a recreational amphetamine overdose), so periods of extended use require increasingly larger doses of the drug in order to achieve the same effect.

Biomolecular mechanisms

Current models of addiction from chronic drug use involve alterations in gene expression in certain parts of the brain, particularly the nucleus accumbens. The most important transcription factors that produce these alterations are ΔFosB, cAMP response element binding protein (CREB), and nuclear factor kappa B (NF-κB). ΔFosB plays a crucial role in the development of drug addictions, since its overexpression in D1-type medium spiny neurons in the nucleus accumbens is necessary and sufficient for most of the behavioral and neural adaptations that arise from addiction. Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression. It has been implicated in addictions to alcohol, cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol, and substituted amphetamines, among others.

ΔJunD, a transcription factor, and G9a, a histone methyltransferase enzyme, both directly oppose the induction of ΔFosB in the nucleus accumbens (i.e., they oppose increases in its expression). Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB). ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise. Since both natural rewards and addictive drugs induce expression of ΔFosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction. Consequently, ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced sex addictions, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use. These sex addictions are associated with a dopamine dysregulation syndrome which occurs in some patients taking dopaminergic drugs.

The effects of amphetamine on gene regulation are both dose- and route-dependent. Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses. The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor. This suggests that medical use of amphetamine does not significantly affect gene regulation.

Pharmacological treatments

As of May 2014, there is no effective pharmacotherapy for amphetamine addiction. Amphetamine addiction is largely mediated through increased activation of dopamine receptors and co-localized NMDA receptors in the nucleus accumbens; magnesium ions inhibit NMDA receptors by blocking the receptor calcium channel. One review suggested that, based upon animal testing, pathological (addiction-inducing) amphetamine use significantly reduces the level of intracellular magnesium throughout the brain. Supplemental magnesium treatment has been shown to reduce amphetamine self-administration (i.e., doses given to oneself) in humans, but it is not an effective monotherapy for amphetamine addiction.

Behavioral treatments

Cognitive behavioral therapy is currently the most effective clinical treatment for psychostimulant addictions. Additionally, research on the neurobiological effects of physical exercise suggests that daily aerobic exercise, especially endurance exercise (e.g., marathon running), prevents the development of drug addiction and is an effective adjunct therapy (i.e., a supplemental treatment) for amphetamine addiction. Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions. In particular, aerobic exercise decreases psychostimulant self-administration, reduces the reinstatement (i.e., relapse) of drug-seeking, and induces increased dopamine receptor D₂ (DRD2) density in the striatum. This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density.

Summary of addiction-related plasticity

Form of neural or behavioral plasticity	Type of reinforcer						Sources
	Opiates	Psycho­stimulants	High fat or sugar food	Sexual reward	Physical exercise (aerobic)	Environmental enrichment
ΔFosB expression in nucleus accumbens D1-type MSNs	↑	↑	↑	↑	↑	↑
Behavioral plasticity
Escalation of intake	Yes	Yes	Yes
Psychostimulant cross-sensitization	Yes	Not applicable	Yes	Yes	Attenuated	Attenuated
Psychostimulant self-administration	↑	↑	↓		↓	↓
Psychostimulant conditioned place preference	↑	↑	↓	↑	↓	↑
Reinstatement of drug-seeking behavior	↑	↑			↓	↓
Neurochemical plasticity
CREB phosphorylation in the nucleus accumbens	↓	↓	↓		↓	↓
Sensitized dopamine response in the nucleus accumbens	No	Yes	No	Yes
Altered striatal dopamine signaling	↓DRD2, ↑DRD3	↑DRD1, ↓DRD2, ↑DRD3	↑DRD1, ↓DRD2, ↑DRD3		↑DRD2	↑DRD2
Altered striatal opioid signaling	↑μ-opioid receptors	↑μ-opioid receptors ↑κ-opioid receptors	↑μ-opioid receptors	↑μ-opioid receptors	No change	No change
Changes in striatal opioid peptides	↑dynorphin	↑dynorphin	↓enkephalin		↑dynorphin	↑dynorphin
Mesocorticolimbic synaptic plasticity
Number of dendrites in the nucleus accumbens	↓	↑		↑
Dendritic spine density in the nucleus accumbens	↓	↑		↑

Dependence and withdrawal

According to another Cochrane Collaboration review on withdrawal in individuals who compulsively use amphetamine and methamphetamine, "when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose." This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week. Amphetamine withdrawal symptoms can include anxiety, drug craving, depressed mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and lucid dreams. The review indicated that withdrawal symptoms are associated with the degree of dependence, suggesting that therapeutic use would result in far milder discontinuation symptoms. Manufacturer prescribing information does not indicate the presence of withdrawal symptoms following discontinuation of amphetamine use after an extended period at therapeutic doses.

Toxicity and psychosis

See also: Stimulant psychosis

In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized by reduced transporter and receptor function. There is no evidence that amphetamine is directly neurotoxic in humans. However, large doses of amphetamine may cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.

A severe amphetamine overdose can result in a stimulant psychosis that may involve a variety of symptoms, such as paranoia and delusions. A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about 5–15% of users fail to recover completely. According to the same review, there is at least one trial that shows antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Psychosis very rarely arises from therapeutic use.

Interactions

See also: Amphetamine § Contraindications

Many types of substances are known to interact with amphetamine, resulting in altered drug action or metabolism of amphetamine, the interacting substance, or both. Inhibitors of the enzymes that metabolize amphetamine (e.g., CYP2D6 and flavin-containing monooxygenase 3) will prolong its elimination half-life, meaning that its effects will last longer. Amphetamine also interacts with MAOIs, particularly monoamine oxidase A inhibitors, since both MAOIs and amphetamine increase plasma catecholamines (i.e., norepinephrine and dopamine); therefore, concurrent use of both is dangerous. Amphetamine modulates the activity of most psychoactive drugs. In particular, amphetamine may decrease the effects of sedatives and depressants and increase the effects of stimulants and antidepressants. Amphetamine may also decrease the effects of antihypertensives and antipsychotics due to its effects on blood pressure and dopamine respectively. In general, there is no significant interaction when consuming amphetamine with food, but the pH of gastrointestinal content and urine affects the absorption and excretion of amphetamine, respectively. Acidic substances reduce the absorption of amphetamine and increase urinary excretion, and alkaline substances do the opposite. Due to the effect pH has on absorption, amphetamine also interacts with gastric acid reducers such as proton pump inhibitors and H₂ antihistamines, which increase gastrointestinal pH (i.e., make it less acidic).

Pharmacology

Pharmacodynamics

For a simpler and less technical explanation of amphetamine's mechanism of action, see Adderall#Mechanism of action.

Pharmacodynamics of amphetamine in a dopamine neuron

via AADC

Amphetamine enters the presynaptic neuron across the neuronal membrane or through DAT. Once inside, it binds to TAAR1 or enters synaptic vesicles through VMAT2. When amphetamine enters the synaptic vesicles through VMAT2, dopamine is released into the cytosol (yellow-orange area). When amphetamine binds to TAAR1, it reduces postsynaptic dopamine receptor firing rate via potassium channels and triggers protein kinase A (PKA) and protein kinase C (PKC) signaling, resulting in DAT phosphorylation. PKA-phosphorylation causes DAT to withdraw into the presynaptic neuron (internalize) and cease transport. PKC-phosphorylated DAT may either operate in reverse or, like PKA-phosphorylated DAT, internalize and cease transport. Amphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a CAMKIIα-dependent pathway, in turn producing dopamine efflux.

Amphetamine exerts its behavioral effects by altering the use of monoamines as neuronal signals in the brain, primarily in catecholamine neurons in the reward and executive function pathways of the brain. The concentrations of the main neurotransmitters involved in reward circuitry and executive functioning, dopamine and norepinephrine, increase dramatically in a dose-dependent manner by amphetamine due to its effects on monoamine transporters. The reinforcing and task saliency effects of amphetamine are mostly due to enhanced dopaminergic activity in the mesolimbic pathway.

Amphetamine has been identified as a potent full agonist of trace amine-associated receptor 1 (TAAR1), a G_s-coupled and G_q-coupled G protein-coupled receptor (GPCR) discovered in 2001, which is important for regulation of brain monoamines. Activation of TAAR1 increases cAMP production via adenylyl cyclase activation and inhibits monoamine transporter function. Monoamine autoreceptors (e.g., D₂ short, presynaptic α₂, and presynaptic 5-HT_1A) have the opposite effect of TAAR1, and together these receptors provide a regulatory system for monoamines. Notably, amphetamine and trace amines bind to TAAR1, but not monoamine autoreceptors. Imaging studies indicate that monoamine reuptake inhibition by amphetamine and trace amines is site specific and depends upon the presence of TAAR1 co-localization in the associated monoamine neurons. As of 2010, co-localization of TAAR1 and the dopamine transporter (DAT) has been visualized in rhesus monkeys, but co-localization of TAAR1 with the norepinephrine transporter (NET) and the serotonin transporter (SERT) has only been evidenced by messenger RNA (mRNA) expression.

In addition to the neuronal monoamine transporters, amphetamine also inhibits both vesicular monoamine transporters, VMAT1 and VMAT2, as well as SLC1A1, SLC22A3, and SLC22A5. SLC1A1 is excitatory amino acid transporter 3 (EAAT3), a glutamate transporter located in neurons, SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes, and SLC22A5 is a high-affinity carnitine transporter. Amphetamine is known to strongly induce cocaine- and amphetamine-regulated transcript (CART) gene expression, a neuropeptide involved in feeding behavior, stress, and reward, which induces observable increases in neuronal development and survival in vitro. The CART receptor has yet to be identified, but there is significant evidence that CART binds to a unique G_i/G_o-coupled GPCR. Amphetamine also inhibits monoamine oxidase at very high doses, resulting in less dopamine and phenethylamine metabolism and consequently higher concentrations of synaptic monoamines. In humans, the only post-synaptic receptor at which amphetamine is known to bind is the 5-HT1A receptor, where it acts as an agonist with micromolar affinity.

The full profile of amphetamine's short-term drug effects is mostly derived through increased cellular communication or neurotransmission of dopamine, serotonin, norepinephrine, epinephrine, histamine, CART peptides, acetylcholine, endogenous opioids, and glutamate, which it effects through interactions with CART, 5-HT1A, EAAT3, TAAR1, VMAT1, and VMAT2.

Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine. Consequently, dextroamphetamine produces greater CNS stimulation than levoamphetamine, roughly three to four times more, but levoamphetamine has slightly stronger cardiovascular and peripheral effects.

Dopamine

In certain brain regions, amphetamine increases the concentration of dopamine in the synaptic cleft. Amphetamine can enter the presynaptic neuron either through DAT or by diffusing across the neuronal membrane directly. As a consequence of DAT uptake, amphetamine produces competitive reuptake inhibition at the transporter. Upon entering the presynaptic neuron, amphetamine activates TAAR1 which, through protein kinase A (PKA) and protein kinase C (PKC) signaling, causes DAT phosphorylation. Phosphorylation by either protein kinase can result in DAT internalization (non-competitive reuptake inhibition), but PKC-mediated phosphorylation alone induces reverse transporter function (dopamine efflux). Amphetamine is also known to increase intracellular calcium, a known effect of TAAR1 activation, which is associated with DAT phosphorylation through a Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent pathway, in turn producing dopamine efflux. Through direct activation of G protein-coupled inwardly-rectifying potassium channels, TAAR1 reduces the firing rate of postsynaptic dopamine receptors, preventing a hyper-dopaminergic state.

Amphetamine is also a substrate for the presynaptic vesicular monoamine transporter, VMAT2. Following amphetamine uptake at VMAT2, the synaptic vesicle releases dopamine molecules into the cytosol in exchange. Subsequently, the cytosolic dopamine molecules exit the presynaptic neuron via reverse transport at DAT.

Norepinephrine

Similar to dopamine, amphetamine dose-dependently increases the level of synaptic norepinephrine, the direct precursor of epinephrine. Based upon neuronal TAAR1 mRNA expression, amphetamine is thought to affect norepinephrine analogously to dopamine. In other words, amphetamine induces TAAR1-mediated efflux and non-competitive reuptake inhibition at phosphorylated NET, competitive NET reuptake inhibition, and norepinephrine release from VMAT2.

Serotonin

Amphetamine exerts analogous, yet less pronounced, effects on serotonin as on dopamine and norepinephrine. Amphetamine affects serotonin via VMAT2 and, like norepinephrine, is thought to phosphorylate SERT via TAAR1. Like dopamine, amphetamine has low, micromolar affinity at the human 5-HT1A receptor.

Other neurotransmitters and peptides

Amphetamine has no direct effect on acetylcholine neurotransmission, but several studies have noted that acetylcholine release increases after its use. In lab animals, amphetamine increases acetylcholine levels in certain brain regions as a downstream effect. In humans, a similar phenomenon occurs via the ghrelin-mediated cholinergic–dopaminergic reward link in the ventral tegmental area. Acute amphetamine administration in humans also increases endogenous opioid release in several brain structures in the reward system.

Extracellular levels of glutamate, the primary excitatory neurotransmitter in the brain, have been shown to increase upon exposure to amphetamine. This cotransmission effect was found in the mesolimbic pathway, an area of the brain implicated in reward, where amphetamine is known to affect dopamine neurotransmission. Amphetamine also induces the selective release of histamine from vesicles in CNS mast cells and efflux from histaminergic neurons through VMAT2.

Pharmacokinetics

The oral bioavailability of amphetamine varies with gastrointestinal pH; it is well absorbed from the gut, and bioavailability is typically over 75% for dextroamphetamine. Amphetamine is a weak base with a pKa of 9–10; consequently, when the pH is basic, more of the drug is in its lipid soluble free base form, and more is absorbed through the lipid-rich cell membranes of the gut epithelium. Conversely, an acidic pH means the drug is predominantly in a water-soluble cationic (salt) form, and less is absorbed. Approximately 15–40% of amphetamine circulating in the bloodstream is bound to plasma proteins.

The half-life of amphetamine enantiomers differ and vary with urine pH. At normal urine pH, the half-lives of dextroamphetamine and levoamphetamine are 9–11 hours and 11–14 hours, respectively. An acidic diet will reduce the enantiomer half-lives to 8–11 hours; an alkaline diet will increase the range to 16–31 hours. The immediate-release and extended release variants of salts of both isomers reach peak plasma concentrations at 3 hours and 7 hours post-dose respectively. Amphetamine is eliminated via the kidneys, with 30–40% of the drug being excreted unchanged at normal urinary pH. When the urinary pH is basic, amphetamine is in its free base form, so less is excreted. When urine pH is abnormal, the urinary recovery of amphetamine may range from a low of 1% to a high of 75%, depending mostly upon whether urine is too basic or acidic, respectively. Amphetamine is usually eliminated within two days of the last oral dose. Apparent half-life and duration of effect increase with repeated use and accumulation of the drug.

The prodrug lisdexamfetamine is not as sensitive to pH as amphetamine when being absorbed in the gastrointestinal tract; following absorption into the blood stream, it is converted by red blood cell-associated enzymes to dextroamphetamine via hydrolysis. The elimination half-life of lisdexamfetamine is generally less than one hour.

CYP2D6, dopamine β-hydroxylase, flavin-containing monooxygenase 3, butyrate-CoA ligase, and glycine N-acyltransferase are the enzymes known to metabolize amphetamine or its metabolites in humans. Amphetamine has a variety of excreted metabolic products, including 4-hydroxyamphetamine, 4-hydroxynorephedrine, 4-hydroxyphenylacetone, benzoic acid, hippuric acid, norephedrine, and phenylacetone. Among these metabolites, the active sympathomimetics are 4‑hydroxyamphetamine, 4‑hydroxynorephedrine, and norephedrine. The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination. The known pathways and detectable metabolites in humans include the following:

Metabolic pathways of amphetamine

4-Hydroxyphenylacetone

Phenylacetone

Benzoic acid

Hippuric acid

Amphetamine

Norephedrine

4-Hydroxyamphetamine

4-Hydroxynorephedrine

Para-
Hydroxylation

Para-
Hydroxylation

Para-
Hydroxylation

Beta-
Hydroxylation

Beta-
Hydroxylation

Oxidative
Deamination

Oxidation

Glycine
Conjugation

The primary active metabolites of amphetamine are 4-hydroxyamphetamine and norephedrine; at normal urine pH, about 30–40% of amphetamine is excreted unchanged and roughly 50% is excreted as the inactive metabolites (bottom row). The remaining 10–20% is excreted as the active metabolites. Benzoic acid is metabolized by butyrate-CoA ligase into an intermediate product, benzoyl-CoA, which is then metabolized by glycine N-acyltransferase into hippuric acid.

Related endogenous compounds

For more details on related compounds, see Trace amines.

Amphetamine has a very similar structure and function to the endogenous trace amines, which are naturally occurring neurotransmitter molecules produced in the human body and brain. Among this group, the most closely related compounds are phenethylamine, the parent compound of amphetamine, and N-methylphenethylamine, an isomer of amphetamine (i.e., it has an identical molecular formula). In humans, phenethylamine is produced directly from L-phenylalanine by the aromatic amino acid decarboxylase (AADC) enzyme, which converts L-DOPA into dopamine as well. In turn, N‑methylphenethylamine is metabolized from phenethylamine by phenylethanolamine N-methyltransferase, the same enzyme that metabolizes norepinephrine into epinephrine. Like amphetamine, both phenethylamine and N‑methylphenethylamine regulate monoamine neurotransmission via TAAR1; unlike amphetamine, both of these substances are broken down by monoamine oxidase B, and therefore have a shorter half-life than amphetamine.

Physical and chemical properties

Racemic amphetamine

Levoamphetamine

Dextroamphetamine

The skeletal structures of L-amph and D-amph

A vial of the colorless amphetamine free base

Amphetamine hydrochloride (left bowl)
Phenyl-2-nitropropene (right cups)

Amphetamine is a methyl homolog of the mammalian neurotransmitter phenethylamine with the chemical formula C₉H₁₃N. The carbon atom adjacent to the primary amine is a stereogenic center, and amphetamine is composed of a racemic 1:1 mixture of two enantiomeric mirror images. This racemic mixture can be separated into its optical isomers: levoamphetamine and dextroamphetamine. Physically, at room temperature, the pure free base of amphetamine is a mobile, colorless, and volatile liquid with a characteristically strong amine odor, and acrid, burning taste. Frequently prepared solid salts of amphetamine include amphetamine aspartate, hydrochloride, phosphate, saccharate, and sulfate, the last of which is the most common amphetamine salt. Amphetamine is also the parent compound of its own structural class, which includes a number of psychoactive derivatives. In organic chemistry, amphetamine is an excellent chiral ligand for the stereoselective synthesis of 1,1'-bi-2-naphthol.

Substituted derivatives

For a more comprehensive list, see Substituted amphetamine.

The substituted derivatives of amphetamine, sometimes referred to as "amphetamines" or "substituted amphetamines", are a broad range of chemicals that contain amphetamine as a "backbone"; specifically, this chemical class includes derivative compounds that are formed by replacing one or more hydrogen atoms in the amphetamine core structure with substituents. The class includes stimulants like methamphetamine, serotonergic empathogens like MDMA, and decongestants like ephedrine, among other subgroups.

Synthesis

For more details on illicit amphetamine synthesis, see Illegal synthesis of substituted amphetamines.

Since the first preparation was reported in 1887, numerous synthetic routes to amphetamine have been developed. The most common route of both legal and illicit amphetamine synthesis employs a non-metal reduction known as the Leuckart reaction (method 1). In the first step, a reaction between phenylacetone and formamide, either using additional formic acid or formamide itself as a reducing agent, yields N-formylamphetamine. This intermediate is then hydrolyzed using hydrochloric acid, and subsequently basified, extracted with organic solvent, concentrated, and distilled to yield the free base. The free base is then dissolved in an organic solvent, sulfuric acid added, and amphetamine precipitates out as the sulfate salt.

A number of chiral resolutions have been developed to separate the two enantiomers of amphetamine. For example, racemic amphetamine can be treated with d-tartaric acid to form a diastereoisomeric salt which is fractionally crystallized to yield dextroamphetamine. Chiral resolution remains the most economical method for obtaining optically pure amphetamine on a large scale. In addition, several enantioselective syntheses of amphetamine have been developed. In one example, optically pure (R)-1-phenyl-ethanamine is condensed with phenylacetone to yield a chiral Schiff base. In the key step, this intermediate is reduced by catalytic hydrogenation with a transfer of chirality to the carbon atom alpha to the amino group. Cleavage of the benzylic amine bond by hydrogenation yields optically pure dextroamphetamine.

A large number of alternative synthetic routes to amphetamine have been developed based on classic organic reactions. One example is the Friedel–Crafts alkylation of chlorobenzene by allyl chloride to yield beta chloropropylbenzene which is then reacted with ammonia to produce racemic amphetamine (method 2). Another example employs the Ritter reaction (method 3). In this route, allylbenzene is reacted acetonitrile in sulfuric acid to yield an organosulfate which in turn is treated with sodium hydroxide to give amphetamine via an acetamide intermediate. A third route starts with ethyl 3-oxobutanoate which through a double alkylation with methyl iodide followed by benzyl chloride can be converted into 2-methyl-3-phenyl-propanoic acid. This synthetic intermediate can be transformed into amphetamine using either a Hofmann or Curtius rearrangement (method 4).

A significant number of amphetamine syntheses feature a reduction of a nitro, imine, oxime or other nitrogen-containing functional groups. In one such example, a Knoevenagel condensation of benzaldehyde with nitroethane yields phenyl-2-nitropropene. The double bond and nitro group of this intermediate is reduced using either catalytic hydrogenation or by treatment with lithium aluminium hydride (method 5). Another method is the reaction of phenylacetone with ammonia, producing an imine intermediate that is reduced to the primary amine using hydrogen over a palladium catalyst or lithium aluminum hydride (method 6).

Amphetamine synthetic routes

Method 1: Synthesis by the Leuckart reaction   Top: Chiral resolution of amphetamine Bottom: Stereoselective synthesis of amphetamine Method 2: Synthesis by Friedel–Crafts alkylation

Method 3: Ritter synthesis Method 4: Synthesis via Hofmann and Curtius rearrangements Method 5: Synthesis by Knoevenagel condensation Method 6: Synthesis using phenylacetone and ammonia

Detection in body fluids

Amphetamine is frequently measured in urine or blood as part of a drug test for sports, employment, poisoning diagnostics, and forensics. Techniques such as immunoassay, which is the most common form of amphetamine test, may cross-react with a number of sympathomimetic drugs. Chromatographic methods specific for amphetamine are employed to prevent false positive results. Chiral separation techniques may be employed to help distinguish the source of the drug, whether prescription amphetamine, prescription amphetamine prodrugs, (e.g., selegiline), over-the-counter drug products (e.g., the American version of Vicks VapoInhaler, which contains levomethamphetamine) or illicitly obtained substituted amphetamines. Several prescription drugs produce amphetamine as a metabolite, including benzphetamine, clobenzorex, famprofazone, fenproporex, lisdexamfetamine, mesocarb, methamphetamine, prenylamine, and selegiline, among others. These compounds may produce positive results for amphetamine on drug tests. Amphetamine is generally only detectable by a standard drug test for approximately 24 hours, although a high dose may be detectable for two to four days.

For the assays, a study noted that an enzyme multiplied immunoassay technique (EMIT) assay for amphetamine and methamphetamine may produce more false positives than liquid chromatography–tandem mass spectrometry. Gas chromatography–mass spectrometry (GC–MS) of amphetamine and methamphetamine with the derivatizing agent (S)-(−)-trifluoroacetylprolyl chloride allows for the detection of methamphetamine in urine. GC–MS of amphetamine and methamphetamine with the chiral derivatizing agent Mosher's acid chloride allows for the detection of both dextroamphetamine and dextromethamphetamine in urine. Hence, the latter method may be used on samples that test positive using other methods to help distinguish between the various sources of the drug.

History, society, and culture

Main article: History and culture of substituted amphetamines

Global estimates of illegal drug users in 2013
(in millions of users)

Substance	Best estimate	Low estimate	High estimate
Amphetamine- type stimulants	33.90	13.87	53.81
Cannabis	181.79	128.48	232.07
Cocaine	17.04	13.80	20.73
Ecstasy	18.79	9.34	28.39
Opiates	16.53	12.92	20.46
Opioids	32.42	27.99	37.56

Amphetamine was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine; its stimulant effects remained unknown until 1927, when it was independently resynthesized by Gordon Alles and reported to have sympathomimetic properties. Amphetamine had no pharmacological use until 1934, when Smith, Kline and French began selling it as an inhaler under the trade name Benzedrine as a decongestant. During World War II, amphetamine and methamphetamine were used extensively by both the Allied and Axis forces for their stimulant and performance-enhancing effects. As the addictive properties of the drug became known, governments began to place strict controls on the sale of amphetamine. For example, during the early 1970s in the United States, amphetamine became a schedule II controlled substance under the Controlled Substances Act. In spite of strict government controls, amphetamine has been used legally or illicitly by people from a variety of backgrounds, including authors, musicians, mathematicians, and athletes.

Amphetamine is still illegally synthesized today in clandestine labs and sold on the black market, primarily in European countries. Among European Union (EU) member states, 1.2 million young adults used illicit amphetamine or methamphetamine in 2013. During 2012, approximately 5.9 metric tons of illicit amphetamine were seized within EU member states; the "street price" of illicit amphetamine within the EU ranged from €6–38 per gram during the same period. Outside Europe, the illicit market for amphetamine is much smaller than the market for methamphetamine and MDMA.

Legal status

As a result of the United Nations 1971 Convention on Psychotropic Substances, amphetamine became a schedule II controlled substance, as defined in the treaty, in all (183) state parties. Consequently, it is heavily regulated in most countries. Some countries, such as South Korea and Japan, have banned substituted amphetamines even for medical use. In other nations, such as Canada (schedule I drug), the Netherlands (List I drug), (Dutch) the United States (schedule II drug), Thailand (category 1 narcotic), and United Kingdom (class B drug), amphetamine is in a restrictive national drug schedule that allows for its use as a medical treatment.

Pharmaceutical products

Two currently prescribed amphetamine formulations that contain both enantiomers are Adderall and Evekeo, the latter of which is racemic amphetamine sulfate. Amphetamine is also prescribed in enantiopure and prodrug form as dextroamphetamine and lisdexamfetamine respectively. Lisdexamfetamine is structurally different from amphetamine, and is inactive until it metabolizes into dextroamphetamine. The free base of racemic amphetamine was previously available as Benzedrine, Psychedrine, and Sympatedrine. Levoamphetamine was previously available as Cydril. Many current amphetamine pharmaceuticals are salts due to the comparatively high volatility of the free base. Some of the current brands and their generic equivalents are listed below.

Amphetamine pharmaceuticals Brand name United States Adopted Name (D:L) ratio of salts Dosage form Source Adderall – 3:1 tablet Adderall XR – 3:1 capsule Dyanavel XR amphetamine suspension Evekeo amphetamine sulfate 1:1 tablet Dexedrine dextroamphetamine sulfate 1:0 capsule ProCentra dextroamphetamine sulfate 1:0 liquid Zenzedi dextroamphetamine sulfate 1:0 tablet Vyvanse lisdexamfetamine dimesylate 1:0 capsule

The skeletal structure of lisdexamfetamine

Amphetamine base in marketed amphetamine medications

drug		formula	molecular weight		amphetamine base			amphetamine base equivalence
			(g/mol)		(percent)			(30 mg dose)
			total	base	total	dextro-	levo-	dextro-	levo-
amphetamine sulfate		(C9H13N)2 • H2SO4	368.49	270.41	73.4%	36.7%	36.7%	11.0 mg	11.0 mg
dextroamphetamine sulfate		(C9H13N)2 • H2SO4	368.49	270.41	73.4%	73.4%	—	22.0 mg	—
Adderall					62.6%	47.5%	15.1%	14.2 mg	4.5 mg
25%	dextroamphetamine sulfate	(C9H13N)2 • H2SO4	368.49	270.41	73.4%	73.4%	—
25%	amphetamine sulfate	(C9H13N)2 • H2SO4	368.49	270.41	73.4%	36.7%	36.7%
25%	dextroamphetamine saccharate	(C9H13N)2 • C6H10O8	480.55	270.41	56.3%	56.3%	—
25%	amphetamine aspartate monohydrate	(C9H13N) • C4H7NO4 • H2O	286.32	135.21	47.2%	23.6%	23.6%
lisdexamfetamine dimesylate		C15H25N3O • (CH4O3S)2	455.49	135.21	29.7%	29.7%	—	8.9 mg	—

Notes

Image legend

Reference notes

References

External links

• CID 3007 from PubChem – Amphetamine
• CID 5826 from PubChem – Dextroamphetamine
• CID 32893 from PubChem – Levoamphetamine
• Comparative Toxicogenomics Database entry: Amphetamine
• Comparative Toxicogenomics Database entry: CARTPT

UpToDate Contents

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• 1. 小児および思春期における類似麻薬の乱用 designer drugs of abuse in children and adolescents
• 2. 高血圧緊急症の治療 treatment of specific hypertensive emergencies
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• 4. 小児および思春期における注意欠陥多動性障害 ：薬物治療 attention deficit hyperactivity disorder in children and adolescents treatment with medications
• 5. 覚せい剤中毒 methamphetamine intoxication

English Journal

• Amphetamine and other pharmacological agents in human and animal studies of recovery from stroke.

• Walker-Batson D1, Mehta J2, Smith P3, Johnson M4.
• Progress in neuro-psychopharmacology & biological psychiatry.Prog Neuropsychopharmacol Biol Psychiatry.2016 Jan 4;64:225-30. doi: 10.1016/j.pnpbp.2015.04.002. Epub 2015 Apr 18.
• Neuromodulation with pharmacological agents, including drugs of abuse such as amphetamine, when paired with behavioral experience, has been shown to positively modify outcomes in animal models of stroke. A number of clinical studies have tested the efficacy of a variety of drugs to enhance recovery
• PMID 25896190

• Long-term effects of repeated social stress on the conditioned place preference induced by MDMA in mice.

• García-Pardo MP1, Blanco-Gandía MC1, Valiente-Lluch M1, Rodríguez-Arias M1, Miñarro J1, Aguilar MA2.
• Progress in neuro-psychopharmacology & biological psychiatry.Prog Neuropsychopharmacol Biol Psychiatry.2015 Dec 3;63:98-109. doi: 10.1016/j.pnpbp.2015.06.006. Epub 2015 Jun 18.
• Previous studies have demonstrated that social defeat stress increases the rewarding effects of psychostimulant drugs such as cocaine and amphetamine. In the present study we evaluated the long-term effects of repeated social defeat (RSD) on the rewarding effects of ±3,4-methylenedioxymethamphetami
• PMID 26093344

• Mice heterozygous for cathepsin D deficiency exhibit mania-related behavior and stress-induced depression.

• Zhou R1, Lu Y1, Han Y1, Li X1, Lou H1, Zhu L1, Zhen X2, Duan S3.
• Progress in neuro-psychopharmacology & biological psychiatry.Prog Neuropsychopharmacol Biol Psychiatry.2015 Dec 3;63:110-8. doi: 10.1016/j.pnpbp.2015.06.007. Epub 2015 Jun 16.
• Mutations in cathepsin D (CTSD), an aspartic protease in the endosomal-lysosomal system, underlie congenital neuronal ceroid-lipofuscinosis (cNCL, also known as CLN10), a devastating neurodegenerative disease. CLN10 patients die within the first few days of life, and in the few patients who live int
• PMID 26092248

Japanese Journal

• Simultaneous Analysis of Benzphetamine and Its Metabolites, and Quantitation of Urinary p-Hydroxy-N-benzylamphetamine by Micellar Electrokinetic Chromatography

• FUJINAMI Aya,MIYAZAWA Tadashi,TAGAWA Noriko,KOBAYASHI Yoshiharu
• Biological & pharmaceutical bulletin 21(11), 1207-1210, 1998-11-15
• … We developed a method for simultaneous analysis of benzphetamine (BZ) and its metabolites, p-hydroxy-N-benzylamphetamine (pHBA), p-hydroxybenzphetamine (pHBZ), amphetamine (AP), methamphetamine and p-hydroxymethamphetamine by micellar electrokinetic chromatography (MEKC). … The effects of acetonitrile and sodium dodecyl sulfate in the running buffer of MEKC on the separation of BZ and its metabolites are also reported. …
• NAID 110003639265

• Results of the NCTR Collaborative Behavioral Teratology Study (CBTS)

• BUELKE-SAM Judy
• 先天異常 27(2), 125-138, 1987-06-30
• NAID 110002787026

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関連記事	「sulfate」「sulfated」「sulfa」「amphetamine」

「sulfate」

　　[★]

• n.

• (官能基やイオンを表して)硫酸、(化合物)硫酸塩、硫酸エステル、硫酸化する

関

H2SO4、inorganic sulfate、sulfate ester、sulfated、sulfation、sulfuric acid、sulfuric acid ester、sulphate、sulphuric acid

　 　

「sulfated」

　　[★]

• adj.

• 硫酸化の

関

sulfate、sulfation、sulphate

「sulfa」

　　[★]

スルファ、サルファ

「amphetamine」

　　[★] アンフェタミン