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use recreational drugs (同)do drugs
administer a drug to; "They drugged the kidnapped tourist" (同)dose
a substance that is used as a medicine or narcotic

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『薬』,薬品,薬剤 / 『麻薬』,麻酔剤 / 〈人〉‘に'薬(特に麻酔剤)を与える / 〈飲食物〉‘に'(麻酔薬・毒薬などの)薬を混ぜる

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/04/17 23:51:28」(JST)

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Epinephrine

Norepinephrine

Dopamine

Chemical structures of catecholamines.

Sympathomimetic drugs mimic the effects of transmitter substances of the sympathetic nervous system such as catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine, etc. Such drugs are used to treat cardiac arrest and low blood pressure, or even delay premature labor, among other things.

These drugs act at the postganglionic sympathetic terminal,^[1] either directly activating postsynaptic receptors, blocking breakdown and reuptake, or stimulating production and release of catecholamines.

1 Mechanisms of action
2 Structure-activity relationship
- 2.1 Direct-acting
  - 2.1.1 Adrenergic receptor agonists
  - 2.1.2 Dopaminergic agonists
- 2.2 Indirect-acting
  - 2.2.1 Norepinephrine and Dopamine transporter blockade
3 Structure-activity relationship
4 Cross-reactivity
5 Comparison
6 Examples
7 See also
8 References
9 External links

Mechanisms of action

The mechanisms of sympathomimetic drugs can be direct-acting, such as α-adrenergic agonists, β-adrenergic agonists, and dopaminergic agonists; or indirect-acting, such as MAOIs, COMT inhibitors, release stimulants, and reuptake inhibitors that increase the levels of endogenous catecholamines.

Structure-activity relationship

For maximum sympathomimetic activity a drug must have the following; 1. Amine group two carbons away from an aromatic group. 2. A hydroxyl group at the chiral beta position in the R-configuration 3. Hydroxyl groups in the meta and para position of the aromatic ring to form a Catechol which is essential for receptor binding

The structure can be modified to alter binding. If the amine is primary or secondary it will have direct action, but if the amine is tertiary it will have poor direct action. Also if the amine has bulky substituents then it will have greater Beta adrenergic receptor activity, but it the substituent is non-bulky then it will favor the alpha adrenergic receptors.

Direct-acting

Adrenergic receptor agonists

Main article: Adrenergic agonist

Direct stimulation of the α- and β-adrenergic receptors can produce sympathomimetic effects. Salbutamol is a very commonly used direct-acting β₂-agonist. Other examples include phenylephrine, isoproterenol, and dobutamine.

Dopaminergic agonists

Stimulation of the D1 receptor by dopaminergic agonists such as fenoldopam is used intravenously to treat hypertensive crisis.

Indirect-acting

Norepinephrine and Dopamine transporter blockade

Classical sympathomimetic drugs are amphetamines (including MDMA), ephedrine, and cocaine, which act by blocking and reversing norepinephrine transporter (NET) activity. NET is a transport protein expressed on the surface of some cells that clears noradrenaline and adrenaline from the extracellular space and into cells, terminating the signaling effects.

Structure-activity relationship

A primary or secondary aliphatic amine separated by 2 carbons from a substituted benzene ring is minimally required for high agonist activity. The pKa of the amine is approximately 8.5-10.^[2] 1- Substitution on aromatic ring-

The presence of hydroxy group in the benzene ring at 3rd and 4th position shows maximum alpha and beta activity

Cross-reactivity

Substances like cocaine also affect dopamine, and some substances like MDMA affect serotonin.

Norepinephrine is synthesized by the body into epinephrine, causing central nervous system stimulation. Thus, all sympathomimetic amines fall into the larger group of stimulants (see psychoactive drug chart). Many of these stimulants have therapeutic use and abuse potential, can induce tolerance, and possibly physical dependence. Stimulates do not produce physical dependence in a way like opioids or sedatives will. The symptoms of physical withdrawal from stimulates are commonly described as being tired, sluggish, or general non-motivation. Physical withdrawal from most Sedatives can be potentially lethal. Opioid withdrawal is very uncomfortable, often describes as a bad case of the flu, but not lethal unless the user has an underlying condition.

Comparison

"Parasympatholytic" and "sympathomimetic" are similar, but not identical. For example, both cause mydriasis, but parasympatholytics reduce accommodation (cycloplegia) while sympathomimetics do not.

Examples

ephedrine (found in Ephedra)
pseudoephedrine (also found in Ephedra species)
amphetamine
methamphetamine
methylphenidate (Ritalin)
lisdexamfetamine (Vyvanse)
cocaine (found in Erythroxylum coca, Coca)
cathinone (found in Catha edulis, Khat)
cathine (also found in Catha edulis)
methcathinone
benzylpiperazine (BZP)
methylenedioxypyrovalerone (MDPV)
4-methylaminorex
pemoline (Cylert)
phenmetrazine (Preludin)
propylhexedrine (Benzedrex)

References

^ "Dorlands Medical Dictionary:sympathomimetic".
^ Medicinal Chemistry of Adrenergics and Cholinergics

External links

Amines, Sympathomimetic at the US National Library of Medicine Medical Subject Headings (MeSH)
Sympathomimetic+amine at eMedicine Dictionary
Sympathomimetic at eMedicine Dictionary

UpToDate Contents

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1. 成人における薬物中毒への一般的アプローチ general approach to drug poisoning in adults
2. 薬物アレルギー患者へのアプローチ an approach to the patient with drug allergy
3. 抗マラリア剤：概要 antimalarial drugs an overview
4. 薬物熱 drug fever
5. ドラッグを注射している患者における肺疾患の概要 overview of pulmonary disease in injection drug users

English Journal

Disparities and guideline adherence in drugs of abuse screening in intracerebral hemorrhage.

Tormoehlen LM1, Blatsioris AD1, Moser EA1, Carter RJ1, Stevenson A1, Ofner S1, Hulin AL1, O'Neill DP1, Cohen-Gadol AA1, Leipzig TJ1, Williams LS1, Mackey J2.
Neurology.Neurology.2016 Dec 7. pii: 10.1212/WNL.0000000000003505. [Epub ahead of print]
OBJECTIVE: To characterize the pattern of urine drug screening in a cohort of intracerebral hemorrhage (ICH) patients at our academic centers.METHODS: We identified cases of primary ICH occurring from 2009 to 2011 in our academic centers. Demographic data, imaging characteristics, processes of care,
PMID 27927933

Predictors of shunt insertion in aneurysmal subarachnoid hemorrhage.

Motiei-Langroudi R1, Adeeb N1, Foreman PM2, Harrigan MR2, Fisher WS Rd2, Vyas NA3, Lipsky RH3, Walters BC4, Tubbs SR5, Shoja MM6, Moore JM1, Gupta R1, Ogilvy CS1, Thomas AT1, Griessenauer CJ7.
World neurosurgery.World Neurosurg.2016 Nov 24. pii: S1878-8750(16)31240-2. doi: 10.1016/j.wneu.2016.11.092. [Epub ahead of print]
OBJECTS: Hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH) requiring permanent cerebrospinal fluid (CSF) diversion in up to two thirds of patients. Factors that predict permanent CSF diversion are not well established.METHODS: An exploratory analysis of 149 patients
PMID 27890755

The effects of Δ9-tetrahydrocannabinol on the dopamine system.

Bloomfield MA1,2,3,4,5, Ashok AH1,2,4, Volkow ND6, Howes OD1,2,4.
Nature.Nature.2016 Nov 16;539(7629):369-377. doi: 10.1038/nature20153.
The effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, are a pressing concern for global mental health. Patterns of cannabis use are changing drastically owing to legalization, the availability of synthetic analogues (commonly termed spice), cannavaping and an e
PMID 27853201

Japanese Journal

In-vitro Recording of Adult Zebrafish Heart Electrocardiogram—A Platform for Pharmacological Testing

, , ,
Journal of Arrhythmia 27(Supplement), OP32_2, 2011
… We found that sympathomimetic drug isoproterenol increased HR, whereas L-type calcium channel blocker verapamil decreased HR. …
NAID 130002129922