protriptyline

プロトリプチリン 　

WordNet

1. tricyclic antidepressant used to treat clinical depression

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/26 10:06:18」(JST)

wiki en

[Wiki en表示]

Protriptyline

Systematic (IUPAC) name
3-(5H-dibenzo[a,d][7]annulen-5-yl)-N-methylpropan-1-amine
Clinical data
Trade names	Vivactil
AHFS/Drugs.com	monograph
MedlinePlus	a604025
Pregnancy category	US: C (Risk not ruled out)
Legal status	℞ (Prescription only)
Routes of administration	Oral
Pharmacokinetic data
Metabolism	Hepatic
Biological half-life	54-92 hours
Excretion	Urine
Identifiers
CAS Number	438-60-8 Y
ATC code	N06AA11
PubChem	CID: 4976
IUPHAR/BPS	7285
DrugBank	DB00344 Y
ChemSpider	4805 Y
UNII	4NDU154T12 Y
ChEBI	CHEBI:8597 Y
ChEMBL	CHEMBL668 Y
Chemical data
Formula	C19H21N
Molecular mass	263.377 g/mol
SMILES c3cc2c(\C=C/c1c(cccc1)C2CCCNC)cc3
InChI InChI=1S/C19H21N/c1-20-14-6-11-19-17-9-4-2-7-15(17)12-13-16-8-3-5-10-18(16)19/h2-5,7-10,12-13,19-20H,6,11,14H2,1H3 Y Key:BWPIARFWQZKAIA-UHFFFAOYSA-N Y
Y (what is this?)  (verify)

Protriptyline (Vivactil) is a tricyclic antidepressant (TCA), specifically a secondary amine, indicated for the treatment of depression and ADHD. Unique among the TCAs, protriptyline tends to be energizing instead of sedating, and is sometimes used for narcolepsy to achieve a wakefulness-promoting effect.

TCAs including protriptyline are also used to reduce the incidence of recurring headaches such as migraine, and for other types of chronic pain. This drug can also be used for sleep apnea treatment along with a carbonic anhydrase inhibitor.

Its sale was discontinued in the UK, Australia, and Republic of Ireland in 2000.

Purpose

Protriptyline is used primarily to treat depression and to treat the combination of symptoms of anxiety and depression. Like most antidepressants of this chemical and pharmacological class, protriptyline has also been used in limited numbers of patients to treat panic disorder, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, enuresis, eating disorders such as bulimia nervosa, cocaine dependency, and the depressive phase of bipolar disorder (manic-depressive) disorder. It has also been used to support smoking cessation programs.

Description

Protriptyline hydrochloride, a dibenzocycloheptene derivative, has a molecular weight of 299.84 g/mol. It is a white to yellowish powder that is freely soluble in water and soluble in dilute HCl. Protriptyline hydrochloride is supplied as 5 mg or 10 mg tablets. Inactive ingredients are anhydrous lactose, colloidal silicon dioxide, magnesium stearate, and microcrystalline cellulose.

Mechanism of action

Protriptyline acts by decreasing the reuptake of norepinephrine and to a lesser extent serotonin (5-HT) in the brain. Tricyclic antidepressants act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Protriptyline increases the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, blocks the action of another brain chemical, acetylcholine. The therapeutic effects of protriptyline, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug.

Protriptyline is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic.

Withdrawal

Though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaise.

Recommended dosage

Protriptyline is available as 5 mg and 10 mg tablets. Doses range from 15 to 40 mg per day and can be taken in one daily dose or divided into up to four doses daily. Some people with severe depression may require up to 60 mg per day. In adolescents and people over age 60, therapy should be initiated at a dose of 5 mg three times a day and increased under supervision of a physician as needed. Patients over age 60 who are taking daily doses of 20 mg or more should be closely monitored for side effects such as rapid heart rate and urinary retention.

Precautions

Like all tricyclic antidepressants, protriptyline should be used cautiously and with close physician supervision. This is especially so in the elderly, or people who have benign prostatic hypertrophy (enlarged prostate gland), or urinary retention, or glaucoma, especially angle-closure glaucoma (the most severe form). Before starting treatment, people should discuss the relative risks and benefits of treatment with their doctors to help determine if protriptyline is the right antidepressant for them. A common problem with tricyclic antidepressants is sedation (drowsiness, lack of physical and mental alertness), but protriptyline is considered the least sedating agent among this class of agents. Its side effects are especially noticeable early in therapy. In most people, early tricyclic side-effects decrease or disappear entirely with time, but, until then, patients taking protriptyline should take care to assess which side-effects occur in them and should not perform hazardous activities requiring mental acuity or coordination. The side-effects are increased when protriptyline is taken with central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines, as well as with other anti-depressants including SSRIs, SNRIs or MonoAmineOxidase Inhibitors. It may be dangerous to take protriptyline in combination with these substances. Protriptyline may increase the possibility of having seizures.

Protriptyline may increase heart rate and stress on the heart. It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug or other antidepressants in the same pharmacological class. In rare cases in which patients with cardiovascular disease must take protriptyline, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage. When Protriptyline is used to treat the depressive component of schizophrenia, psychotic symptoms may be aggravated. Likewise, in manic-depressive psychosis, depressed patients may experience a shift toward the manic phase if they are treated with an antidepressant drug. Paranoid delusions, with or without associated hostility, may be exaggerated. In any of these circumstances, it may be advisable to reduce the dose of Protriptyline or to use a major tranquilizing drug concurrently.

Side effects

Protriptyline shares side effects common to all tricyclic antidepressants. The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, dizziness, decreased coordination, anxiety, blood disorders, confusion, decreased libido, dizziness, flushing, headache, impotence, insomnia, low blood pressure, nightmares, rapid or irregular heartbeat, rash, seizures, sensitivity to sunlight, stomach and intestinal problems. Other more complicated side effects include; chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling; sudden numbness or weakness, especially on one side of the body; sudden headache, confusion, problems with vision, speech, or balance; hallucinations, or seizure (convulsions); easy bruising or bleeding, unusual weakness; restless muscle movements in your eyes, tongue, jaw, or neck; urinating less than usual or not at all; extreme thirst with headache, nausea, vomiting, and weakness; or feeling light-headed or fainting.

Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief. Men with prostate enlargement who take protriptyline may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant. In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect.

Adverse reactions

Cardiovascular: Myocardial infarction; stroke; heart block; arrhythmias; hypotension, particularly orthostatic hypotension; hypertension; tachycardia; palpitation.

Psychiatric: Confusional states (especially in the elderly) with hallucinations, disorientation, delusions, anxiety, restlessness, agitation; hypomania; exacerbation of psychosis; insomnia, panic, and nightmares.

Neurological: Seizures; incoordination; ataxia; tremors; peripheral neuropathy; numbness, tingling, and paresthesias of extremities; extrapyramidal symptoms; drowsiness; dizziness; weakness and fatigue; headache; syndrome of inappropriate ADH (antidiuretic hormone) secretion;tinnitus; alteration in EEG patterns.

Anticholinergic: Paralytic ileus; hyperpyrexia; urinary retention, delayed micturition, dilatation of the urinary tract; constipation; blurred vision, disturbance of accommodation, increased intraocular pressure, mydriasis; dry mouth and rarely associated sublingual adentitis.

Allergic: Drug fever; petechiae, skin rash, urticaria, itching, photosensitization (avoid excessive exposure to sunlight); edema (general, or of face and tongue).

Hematologic: Agranulocytosis; bone marrow depression; leukopenia;thrombocytopenia; purpura; eosinophilia.

Gastrointestinal: Nausea and vomiting; anorexia; epigastric distress; diarrhea; peculiar taste; stomatitis; abdominal cramps; black tongue.

Endocrine: Impotence, increased or decreased libido: gynecomastia in the male; breast enlargement and galactorrhea in the female; testicular swelling; elevation or depression of blood sugar levels.

Other: Jaundice (simulating obstructive); altered liver function; parotid swelling; alopecia; flushing; weight gain or loss; urinary frequency, nocturia; perspiration.

Overdose

Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose, therefore, hospital monitoring is required as soon as possible. Critical manifestations of overdosage include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia.

Metabolism

Metabolic studies indicate that Protriptyline is well absorbed from the gastrointestinal tract and is rapidly sequestered in tissues. Relatively low plasma levels are found after administration, and only a small amount of unchanged drug is excreted in the urine of dogs and rabbits. Preliminary studies indicate that demethylation of the secondary amine moiety occurs to a significant extent, and that metabolic transformation takes place in the liver. It penetrates the brain rapidly in mice and rats, and moreover that which is present in the brain is almost all unchanged drug. Studies on the disposition of radioactive Protriptyline in human test subjects showed significant plasma levels within 2 hours, peaking at 8 to 12 hours, then declining gradually. Urinary excretion studies in the same subjects showed significant amounts of radioactivity in 2 hours. The rate of excretion was slow. Cumulative urinary excretion during 16 days accounted for approximately 50% of the drug. The fecal route of excretion did not seem to be important.

References

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 三環系抗うつ剤および四環系抗うつ剤：薬理学、投与、および副作用 tricyclic and tetracyclic drugs pharmacology administration and side effects
• 2. 成人における緊張型頭痛：予防的治療 tension type headache in adults preventive treatment
• 3. 成人におけるナルコレプシーの治療 treatment of narcolepsy in adults
• 4. 慢性片頭痛 chronic migraine
• 5. 成人における片頭痛の予防的治療 preventive treatment of migraine in adults

English Journal

• A fully validated method for the simultaneous determination of 11 antidepressant drugs in whole blood by gas chromatography-mass spectrometry.

• Papoutsis I, Khraiwesh A, Nikolaou P, Pistos C, Spiliopoulou C, Athanaselis S.SourceDepartment of Forensic Medicine and Toxicology, School of Medicine, National and Kapodistrian University of Athens, Greece.
• Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2012 May 15. [Epub ahead of print]
• Antidepressant drugs are widely used for the treatment of depression and other psychiatric disorders and as a result they are involved in numerous clinical and forensic cases. The aim of this study was the development, optimization and validation of a simple, specific and sensitive GC/MS method for
• PMID 22658904

• Quantification of Tricyclic Antidepressants Using UPLC-MS/MS.

• Johnson-Davis KL, Juenke JM, Davis R, McMillin GA.SourceARUP Laboratories Inc., Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
• Methods in molecular biology (Clifton, N.J.).Methods Mol Biol.2012;902:175-84.
• Depression is a psychiatric condition that affects about 120 million people worldwide and can interfere with independence and productivity in essentially all aspects of daily life. Depression is also associated with risk of self-harm, and ultimately suicide. Antidepressant medications are widely use
• PMID 22767118

Japanese Journal

• Responce of obstructive sleep apnea to fluoxetine and protriptyline

• HANZAL DA
• Chest 100, 416-421, 1991
• NAID 30030218904

• DRUG DEPENDENCE LIABILITY OF TRICYCLIC ANTIDEPRESSANTS EVALUATED IN MONKEYS

• Yanagita Tomoji,Takahashi Saburo,Oinuma Nagaoki
• 臨床薬理 3(4), 289-294, 1972
• … Drug depenence liabilty of 5 tricyclic antidepressants, imipramine, imipramine-N-oxide, protriptyline, maprotiline and iprindole, were examined using rhesus monkeys. … In gross behavioral observations of acute central nervous system effects in normal monkeys, imipramine, protriptyline, maprotiline and iprindole produced a decrease of awareness, mydriasis, ataxia, tremor and convulsions, but imipramine-N-oxide did not. …
• NAID 130002044077

• 二重盲検法による抗うつ剤Protriptylineの薬効の評価

• 高橋 良 [他]
• 精神医学 13(6), 635-645, 1971-06
• NAID 40017964205

Related Links

• Protriptyline: MedlinePlus Drug Information

Protriptyline comes as a tablet to take by mouth. It is usually taken three or four times a day. Take protriptyline at around the same times every day. Follow the directions on your prescription label carefully, and ask your ...

• Drug Monograph

詳細の表示を試みましたが、サイトのオーナーによって制限されているため表示できません。

Related Pictures

---

★リンクテーブル★

リンク元	「プロトリプチリン」

「プロトリプチリン」

　　[★]

英

protriptyline

化

塩酸プロトリプチリン protriptyline hydrochloride

関

ナルコレプシー]]