From Wikipedia, the free encyclopedia
Amitriptyline (Elavil, Tryptizol) is a psychoactive drug and pharmaceutical of the tricyclic antidepressant (TCA) chemical class which is used primarily as an antidepressant and anxiolytic agent. It is the most widely prescribed TCA and perhaps also the most efficient against depressive symptoms.
[edit] Indications
[edit] Approved
Amitriptyline is approved for the treatment of major depression. (clinical/endogenous depression, also Involutional melancholia 'depression of late life', which is no longer seen as a disease in its own right). Adult typical dosages are 25 to 150 mg daily, with half this initially for elderly or adolescents.
Children between the ages of 7 to 10 years having a dose of 10 to 20 mg, older children 25 to 50 mg at night. It should be gradually withdrawn at the end of the course, which overall should be of no more than 3 months.[1]
Amitriptyline is used in ankylosing spondylitis for pain relief and in some European countries it is officially approved as a preventive for patients with frequent/chronic migraines, usually 25 to 75 mg. It is also used as a preventive for patients with recurring biliary dyskinesia (sphincter of Oddi dysfunction), usually 10 mg daily[2].
[edit] Unapproved / Off-label
Amitriptyline may be prescribed for other conditions such as insomnia, post-traumatic stress disorder (PTSD),[3] migraine, rebound headache, chronic pain, tinnitus, chronic cough, postherpetic neuralgia (persistent pain following a shingles attack), carpal tunnel syndrome (CTS), fibromyalgia, vulvodynia, interstitial cystitis, male chronic pelvic pain syndrome, irritable bowel syndrome (IBS), diabetic peripheral neuropathy, neurological pain, and painful paresthesias related to multiple sclerosis and at low doses as a prophylaxis (preventive) for patients with chronic migraines.[4] Typically lower dosages are required for pain modification of 10 to 50 mg daily.[1]
Amitriptyline in low doses is also sometimes prescribed to help ease the symptoms of chronic fatigue syndrome. It is thought to help combat symptoms of insomnia primarily, in addition to other selected symptoms of the affliction.
A randomized controlled trial published in June 2005 found that amitriptyline was effective in functional dyspepsia that did not respond to a first-line treatment (famotidine or mosapride).[5]
[edit] Pharmacology
Amitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the norepinephrine transporter, and moderate effects on the serotonin transporter.[6][7] It has negligible influence on the dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin.[7]
Amitriptyline additionally functions as a 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, α1-adrenergic, H1, and mACh receptor antagonist, and σ1 receptor agonist.[8][9][10][11] It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine.[12] Amitriptyline inhibits sodium channels, L-type calcium channels, and Kv1.1, Kv7.2, and Kv7.3 voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well.[13][14][15]
Amitriptyline may ease chronic pain through mediation of endogenous opioids in the central nervous system. [16]
Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors.[17] It promotes the heterodimerization of these proteins in the absence of NGF and has potent neurotrophic activity both in-vivo and in-vitro in mouse models.[17]
[edit] Side Effects
Common side effects of using amitriptyline are mostly due to its anticholinergic activity, including: weight gain, dry mouth, loss of appetite, drowsiness, muscle stiffness, nausea, constipation, nervousness, dizziness, blurred vision, urinary retention and insomnia. Some rare side effects include tinnitus, hypotension, mania, psychosis, heart block, arrhythmias, lip and mouth ulcers, extrapyramidal symptoms, depression, and hepatic toxicity.
[edit] Overdose
The symptoms and the treatment of an overdose are largely the same as for the other TCAs.
[edit] See also
[edit] References
- ^ a b British National Formulary 45 (March 2003).
- ^ S. G. Hubscher et al. (2006). Functional biliary type pain syndrome. In P. J. Pasricha, W. D. Willis & G. F. Gebhart (Eds.), ' ' italics' ' Chronic Abdominal and Visceral Pain' 'italics' '. London: Informa Healthcare, pp. 459-461.
- ^ National Institute for Clinical Excellence: The Treatment of PTSD in Adults and Children
- ^ Ziegler D, Hurwitz A, Hassanein R, Kodanaz H, Preskorn S, Mason J (1987). "Migraine prophylaxis. A comparison of propranolol and amitriptyline". Arch Neurol 44 (5): 486–9. PMID 3579659.
- ^ Otaka M, Jin M, Odashima M, et al. (June 2005). "New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline". Aliment. Pharmacol. Ther. 21 (Suppl 2): 42–6. doi:10.1111/j.1365-2036.2005.02473.x. PMID 15943846. http://www.ingentaconnect.com/content/bsc/apt/2005/00000021/A00201s2/art00008.
- ^ http://www.cnsforum.com/content/pictures/imagebank/hirespng/antidep_uptake_specific.png
- ^ a b Tatsumi; Groshan, K; Blakely, RD; Richelson, E (1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". European journal of pharmacology 340 (2-3): 249–58. doi:10.1016/S0014-2999(97)01393-9. PMID 9537821. edit
- ^ Owens; Morgan, WN; Plott, SJ; Nemeroff, CB (1997). "Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites". The Journal of pharmacology and experimental therapeutics 283 (3): 1305–22. PMID 9400006. edit
- ^ Alan F. Schatzberg, Charles B. (2006). Essentials of clinical psychopharmacology. American Psychiatric Pub. p. 7. ISBN 1585622435, 9781585622436.
- ^ Rauser; Savage, JE; Meltzer, HY; Roth, BL (2001). "Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor". The Journal of pharmacology and experimental therapeutics 299 (1): 83–9. PMID 11561066. edit
- ^ Werling; Keller, A.; Frank, J.; Nuwayhid, S. (2007). "A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder". Experimental neurology 207 (2): 248–257. doi:10.1016/j.expneurol.2007.06.013. PMID 17689532. edit
- ^ Sills; Loo, PS (1989). "Tricyclic antidepressants and dextromethorphan bind with higher affinity to the phencyclidine receptor in the absence of magnesium and L-glutamate". Molecular pharmacology 36 (1): 160–5. PMID 2568580. edit
- ^ Pancrazio; Kamatchi, GL; Roscoe, AK; Lynch C, 3rd (1998). "Inhibition of neuronal Na+ channels by antidepressant drugs". The Journal of pharmacology and experimental therapeutics 284 (1): 208–14. PMID 9435180. edit
- ^ Zahradnik, I.; Minarovic, I.; Zahradnikova, A. (2008). "Inhibition of the cardiac L-type calcium channel current by antidepressant drugs". The Journal of pharmacology and experimental therapeutics 324 (3): 977–984. doi:10.1124/jpet.107.132456. PMID 18048694. edit
- ^ Punke MA, Friederich P (May 2007). "Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels". Anesthesia and Analgesia 104 (5): 1256–64, tables of contents. doi:10.1213/01.ane.0000260310.63117.a2. PMID 17456683. http://www.anesthesia-analgesia.org/cgi/pmidlookup?view=long&pmid=17456683.
- ^ Delta-opioid receptors are critical for tricyclic antidepressant treatment of neuropathic allodynia. Benbouzid M, Gavériaux-Ruff C, Yalcin I, Waltisperger E, Tessier LH, Muller A, Kieffer BL, Freund-Mercier MJ, Barrot M. 1: Biol Psychiatry. 2008 Mar 15;63(6):633-6. E http://www.ncbi.nlm.nih.gov/pubmed/17693391
- ^ a b Jang; Liu, X.; Chan, C.; Weinshenker, D.; Hall, R.; Xiao, G.; Ye, K. (2009). "Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity". Chemistry & biology 16 (6): 644–656. doi:10.1016/j.chembiol.2009.05.010. PMID 19549602. edit
[edit] Further reading
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serotonin: (Cianopramine • Clomipramine)
norepinephrine: (Amoxapine, Butriptyline, Desipramine/Lofepramine, Dibenzepin, Dosulepin, Doxepin, Iprindole, Melitracen, Nitroxazepine, Nortriptyline, Protriptyline, Trimipramine)
s+n: ( Amitriptyline#, Imipramine)
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Morpholines: Oxaflozane • Phendimetrazine • Phenmetrazine; Oxazolines: 4-Methylaminorex (4-MAR, 4-MAX) • Aminorex • Clominorex • Cyclazodone • Fenozolone • Fluminorex • Pemoline • Thozalinone; Phenethylamines (also Amphetamines, Cathinones, Phentermines, etc): 2-Hydroxyphenethylamine (2-OH-PEA) • 4-Methylamphetamine (4-MA) • 4-Methylmethamphetamine (4-MMA) • Alfetamine • Amfecloral • Amfepentorex • Amphetamine ( Dextroamphetamine, Levoamphetamine) • Amphetaminil • β-Methylphenethylamine (β-Me-PEA) • Benzodioxolylbutanamine (BDB) • Benzodioxolylhydroxybutanamine (BOH) • Benzphetamine • Buphedrone • Butylone • Cathine • Cathinone • Clobenzorex • Clortermine • Diethylcathinone (Diethylpropion, Amfepramone) • Dimethoxyamphetamine (DMA) • Dimethoxymethamphetamine (DMMA) • Dimethylamphetamine • Dimethylcathinone (Dimethylpropion, Metamfepramone) • Ephedrine (EPH) • Ethcathinone (Ethylpropion) • Ethylamphetamine • Ethylbenzodioxolylbutanamine (EBDB) • Ethylone • Fenethylline • Fenproporex • Flephedrone • Fludorex • Furfenorex • Hordenine • Indanorex • Lisdexamfetamine • Lophophine (Homomyristicylamine) • Mefenorex • Mephedrone • Mephentermine • Methamphetamine (Desoxyephedrine, Methedrine; Dextromethamphetamine, Levomethamphetamine) • Methcathinone (Methylpropion) • Methedrone • Methoxymethylenedioxyamphetamine (MMDA) • Methoxymethylenedioxymethamphetamine (MMDMA) • Methylbenzodioxolylbutanamine (MBDB) • Methylenedioxyamphetamine (MDA; Tenamfetamine) • Methylenedioxyethylamphetamine (MDEA) • Methylenedioxyhydroxyamphetamine (MDOH) • Methylenedioxymethamphetamine (MDMA) • Methylenedioxymethylphenethylamine (MDMPEA; Homarylamine) • Methylenedioxyphenethylamine (MDPEA; Homopiperonylamine) • Methylone • Ortetamine • Parabromoamphetamine (PBA) • Parachloroamphetamine (PCA) • Parafluoroamphetamine (PFA) • Parafluoromethamphetamine (PFMA) • Parahydroxyamphetamine (PHA) • Paraiodoamphetamine (PIA) • Paramethoxyamphetamine (PMA) • Paramethoxyethylamphetamine (PMEA) • Paramethoxymethamphetamine (PMMA) • Paredrine (Norpholedrine, Oxamphetamine) • Phenethylamine (PEA) • Pholedrine • Phenpentermine • Phenpromethamine • Phentermine • Phenylpropanolamine (PPA) • Prenylamine • Propylamphetamine • Pseudoephedrine (PSE) • Tiflorex (Flutiorex) • Tyramine (TRA) • Xylopropamine • Zylofuramine; Piperazines: 2,5-Dimethoxy-4-bromobenzylpiperazine (2C-B-BZP) • Benzylpiperazine (BZP) • Methoxyphenylpiperazine (MeOPP; Paraperazine) • Methylbenzylpiperazine (MBZP) • Methylenedioxybenzylpiperazine (MDBZP; Piperonylpiperazine) • Parafluorophenylpiperazine (pFPP; Fluoperazine); Others: 2-Amino-1,2-dihydronaphthalene (2-ADN) • 2-Aminoindane (2-AI) • 2-Aminotetralin (2-AT) • 2-Benzylpiperidine (2-BP) • 4-Benzylpiperidine (4-BP) • Clofenciclan • Cyclopentamine • Cypenamine • Cyprodenate • Feprosidnine • Gilutensin • Heptaminol • Hexacyclonate • Indanylaminopropane (IAP) • Isometheptene • Methylhexanamine • Naphthylaminopropane (NAP) • Octodrine • Phthalimidopropiophenone • Propylhexedrine (PHX) • Tuaminoheptane (Tuamine)
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Agonists: Glutamate/Acite Site Competitive Agonists: Aspartate • Glutamate • Homoquinolinic Acid • Ibotenic Acid • NMDA • Quinolinic Acid • Tetrazolylglycine; Glycine Site Agonists: ACBD • ACPC • ACPD • Alanine • CCG • Cycloserine • DHPG • Fluoroalanine • Glycine • HA-966 • L-687,414 • Milacemide • Sarcosine • Serine • Tetrazolylglycine; Polyamine Site Agonists: Acamprosate • Spermidine • Spermine
Antagonists: Competitive Antagonists: AP5 (APV) • AP7 • CGP-37849 • CGP-39551 • CGP-39653 • CGP-40116 • CGS-19755 • CPP • LY-233,053 • LY-235,959 • LY-274,614 • MDL-100,453 • Midafotel (d-CPPene) • NPC-12,626 • NPC-17,742 • PBPD • PEAQX • Perzinfotel • PPDA • SDZ-220581 • Selfotel (CGS-19,755); Noncompetitive Antagonists: ARR-15,896 • Caroverine • Dexanabinol (HU-211) • FPL-12495 • FR-115,427 • Hodgkinsine • Magnesium • MDL-27,266 • NPS-1506 • Psychotridine • Zinc; Uncompetitive Pore Blockers: 2-MDP • 8A-PDHQ • Amantadine • Aptiganel (CNS-1102) • ARL-12,495 • ARL-15,896-AR • ARL-16,247 • Budipine • Delucemine • Dexoxadrol • Dieticyclidine • Dizocilpine (MK-801) • Endopsychosin • Esketamine • Etoxadrol • Eticyclidine • Gacyclidine • Ibogaine • Indantadol (CHF-3381) • Ketamine • Ketobemidone • Loperamide • Memantine • Meperidine (Pethidine) • Methadone • Methorphan ( Dextromethorphan, Levomethorphan) • Milnacipran • Morphanol ( Dextrorphan, Levorphanol) • NEFA • Neramexane • Nitrous Oxide • Noribogaine • Orphenadrine • Phencyclamine • Phencyclidine • Propoxyphene • Remacemide • Rhynchophylline • Riluzole • Rimantadine • Rolicyclidine • Tenocyclidine • Tiletamine • Tramadol • Xenon; Glycine Site Antagonists: ACEA-1021 • ACEA-1328 • ACPC • Carisoprodol • CGP-39653 • CKA • DCKA • Felbamate • Gavestinel (GV-150,526) • GV-196,771 • Kynurenic Acid • L-689,560 • L-701,324 • Lacosamide • Licostinel (ACEA-1021) • LU-73,068 • MDL-105,519 • Meprobamate • MRZ 2/576 • PNQX • ZD-9379; NR2B Subunit Antagonists: Besonprodil • CO-101,244 (PD-174,494) • CP-101,606 • Eliprodil • Haloperidol • Ifenprodil • Isoxsuprine • Nylidrin • Ro8-4304 • Ro25-6981 • Traxoprodil; Polyamine Site Antagonists: Arcaine • Co 101676 • Diaminopropane • Diethylenetriamine • Huperzine A • Putrescine • Ro 25-6981; Unclassified/Unsorted Antagonists: Chloroform • Diethyl Ether • Enflurane • Ethanol (Alcohol) • Halothane • Isoflurane • Methoxyflurane
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Agonists: 2-Pyridylethylamine • Betahistine • Histamine • HTMT • UR-AK49
Antagonists: 1st Generation: Alimemazine • Azatadine • Bamipine • Bepotastine • Bromazine • Brompheniramine • Buclizine • Carbinoxamine • Chlorcyclizine • Chloropyramine • Chlorothen • Chlorpheniramine • Chlorphenoxamine • Cinnarizine • Clemastine • Clobenzepam • Clocinizine • Cyclizine • Cyproheptadine • Dacemazine • Deptropine • Dexbrompheniramine • Dexchlorpheniramine • Dimetindene • Diphenhydramine • Diphenylpyraline • Doxylamine • Embramine • Etymemazine • Histapyrrodine • Hydroxyethylpromethazine • Hydroxyzine • Iproheptine • Isopromethazine • Isothipendyl • Meclizine • Mepyramine (Pyrilamine) • Mequitazine • Methafurylene • Methapyrilene • Methdilazine • Moxastine • Niaprazine • Orphenadrine • Oxatomide • Oxomemazine • p-Methyldiphenhydramine • Pheniramine • Phenyltoloxamine • Promethazine • Pyrrobutamine • Setastine • Talastine • Thenalidine • Thenyldiamine • Thiazinamium • Thonzylamine • Tolpropamine • Tripelennamine • Triprolidine; 2nd Generation: Acrivastine • Antazoline • Astemizole • Azatadine • Azelastine • Bamipine • Cetirizine • Clemizole • Clobenztropine • Deptropine • Dimebon • Ebastine • Emedastine • Epinastine • Ketotifen • Levocabastine • Loratadine • Mebhydrolin • Mizolastine • Olopatadine • Phenindamine • Pimethixene • Pyrrobutamine • Rupatadine • Terfenadine • Thenalidine • Tritoqualine; 3rd Generation: Desloratadine • Fexofenadine • Levocetirizine; Miscellaneous: Tricyclic Antidepressants ( Amitriptyline, Doxepin, Trimipramine, etc) • Tetracyclic Antidepressants ( Mianserin, Mirtazapine, etc) • Serotonin Antagonists and Reuptake Inhibitors ( Trazodone, Nefazodone) • Typical Antipsychotics ( Chlorpromazine, Thioridazine, etc) • Atypical Antipsychotics ( Clozapine, Olanzapine, Quetiapine, etc)
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Agonists: Lysergamides: Dihydroergotamine • Methysergide; Triptans: Almotriptan • Eletriptan • Frovatriptan • Naratriptan • Rizatriptan • Sumatriptan • Zolmitriptan; Tryptamines: 5-CT • 5-MT; Others: CP-135,807 • CP-286,601 • GR-46611 • L-694,247 • L-772,405 • PNU-109,291 • PNU-142,633
Antagonists: Lysergamides: Metergoline • Methiothepin; Tryptamines: Rauwolscine • Yohimbine; Others: Alniditan BRL-15572 • GR-127,935 • Ketanserin • LY-310,762 • LY-367,642 • LY-456,219 • LY-456,220 • Ritanserin • Ziprasidone
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Agonists: Phenethylamines: 2C-B • 2C-E • 2C-I • 2C-T-2 • 2C-T-7 • 2C-T-21 • DOB • DOC • DOI • DOM • MDA • MDMA • Mescaline • Myristicin; Piperazines: Aripiprazole • mCPP • TFMPP; Tryptamines: 5-CT • 5-MeO-α-ET • 5-MeO-α-MT • 5-MeO-DET • 5-MeO-DiPT • 5-MeO-DMT • 5-MeO-DPT • 5-MT • α-ET • α-Methyl-5-HT • α-MT • Bufotenin • DET • DiPT • DMT • DPT • Psilocin • Psilocybin; Others: A-372,159 • AL-38022A • CP-809,101 • Lorcaserin • MK-212 • PNU-22394 • Ro60-0175 • Vabicaserin • WAY-629 • WAY-161,503 • YM-348
Antagonists: Atypical Antipsychotics: Clozapine • Iloperidone • Melperone • Olanzapine • Paliperidone • Pimozide • Quetiapine • Risperidone • Sertindole • Ziprasidone • Zotepine; Typical Antipsychotics: Chlorpromazine • Loxapine • Pipamperone; Antidepressants: Agomelatine • Amitriptyline • Amoxapine • Etoperidone • Fluoxetine • Mianserin • Mirtazapine • Nefazodone • Nortriptyline • Trazodone; Others: Cinanserin • Cyproheptadine • Deramciclane • Dimebolin • Dotarizine • Eltoprazine • FR-260,010 • Ketanserin • Ketotifen • Methysergide • Pizotifen • Ritanserin • RS-102,221 • SB-200,646 • SB-206,553 • SB-221,284 • SB-228,357 • SB-242,084 • SB-243,213 • SDZ SER-082 • Xylamidine
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Agonists: Lysergamides: Ergotamine • LSD
Antagonists: Methiothepin
* Note that the 5-HT5B receptor is not functional in humans.
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