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{{Drugbox| Watchedfields = changed
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 321793640
| verifiedrevid = 321793640
| IUPAC_name = 3-(10,11-dihydro- 5''H''-dibenzo[[''a'',''d'']]cycloheptene- 5-ylidene)- ''N'',''N''-dimethyl- 1-propanamine''
| IUPAC_name = 3-(10,11-dihydro- 5''H''-dibenzo[[''a'',''d'']]cycloheptene- 5-ylidene)- ''N'',''N''-dimethyl- 1-propanamine''
| image = Amitriptyline.svg
| image = Amitriptyline.svg
| image2 = Amitriptyline-from-picrate-xtal-3D-balls.png
| image2 = Amitriptyline-from-picrate-xtal-3D-balls.png
| CASNo_Ref = {{cascite}}
| CASNo_Ref = {{cascite}}
| InChI = 1/C20H23N/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h3-6,8-12H,7,13-15H2,1-2H3
| InChI = 1/C20H23N/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h3-6,8-12H,7,13-15H2,1-2H3
| smiles = c3cc2c(/C(c1c(cccc1)CC2)=C\CCN(C)C)cc3
| smiles = c3cc2c(/C(c1c(cccc1)CC2)=C\CCN(C)C)cc3
| InChIKey = KRMDCWKBEZIMAB-UHFFFAOYAI
| InChIKey = KRMDCWKBEZIMAB-UHFFFAOYAI
| CAS_number = 50-48-6
| CAS_number = 50-48-6
| ATC_prefix = N06
| ATC_prefix = N06
| ATC_suffix = AA09
| ATC_suffix = AA09
| PubChem = 2160
| PubChem = 2160
| ChemSpiderID = 2075
| ChemSpiderID = 2075
| DrugBank = APRD00227
| DrugBank = APRD00227
| C = 20 | H = 23 | N = 1
| C = 20 | H = 23 | N = 1
| molecular_weight = 277.403 g/mol
| molecular_weight = 277.403 g/mol
| bioavailability = 30–60% due to first pass metabolism
| bioavailability = 30–60% due to first pass metabolism
| protein_bound = > 90%
| protein_bound = > 90%
| metabolism = [[Hepatic]]<br \>[[CYP2C19]], [[CYP1A2]], [[CYP2D6]]
| metabolism = [[Hepatic]]<br \>[[CYP2C19]], [[CYP1A2]], [[CYP2D6]]
| elimination_half-life = 10–50 hours, with an average of 15 hours
| elimination_half-life = 10–50 hours, with an average of 15 hours
| excretion = [[Renal]]
| excretion = [[Renal]]
| pregnancy_US = D
| pregnancy_US = D
| pregnancy_category =
| pregnancy_category =
⚫
| legal_status = Rx-only
| legal_AU = Unscheduled
⚫
| routes_of_administration = Oral
| legal_UK = POM
| legal_US = Unscheduled
⚫
| legal_status = Unscheduled
⚫
| routes_of_administration= Oral
}}
}}


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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 (medicine)|chronic]] [[migraine]]s, usually 25 to 75&nbsp;mg. It is also used as a preventive for patients with recurring [[biliary dyskinesia]] ([[sphincter of Oddi]] dysfunction), usually 10&nbsp;mg daily<ref name="Hubscher">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.</ref>.
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 (medicine)|chronic]] [[migraine]]s, usually 25 to 75&nbsp;mg. It is also used as a preventive for patients with recurring [[biliary dyskinesia]] ([[sphincter of Oddi]] dysfunction), usually 10&nbsp;mg daily<ref name="Hubscher">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.</ref>.


=== Unapproved / Off-label ===
=== Unapproved/Off-label ===


Amitriptyline may be prescribed for other conditions such as [[insomnia]], [[post-traumatic stress disorder]] (PTSD),<ref>National Institute for Clinical Excellence: [http://www.nice.org.uk/nicemedia/pdf/CG026publicinfo.pdf The Treatment of PTSD in Adults and Children]</ref> [[migraine]], [[rebound headache]], [[chronic pain]], [[tinnitus]], [[chronic cough]], [[postherpetic neuralgia]] (persistent pain following a [[shingles]] attack), [[carpal tunnel syndrome]] (CTS), [[fibromyalgia]], [[vulvodynia]], [[interstitial cystitis]], [[UCPPS|male chronic pelvic pain syndrome]], [[irritable bowel syndrome]] (IBS), [[diabetic neuropathy|diabetic peripheral neuropathy]], [[neurological]] pain, and painful [[paresthesia]]s related to [[multiple sclerosis]] and at low doses as a [[prophylaxis]] (preventive) for patients with [[Chronic (medicine)|chronic]] [[migraine]]s.<ref name="pmid3579659">{{cite journal | author = Ziegler D, Hurwitz A, Hassanein R, Kodanaz H, Preskorn S, Mason J | title = Migraine prophylaxis. A comparison of propranolol and amitriptyline | journal = Arch Neurol | volume = 44 | issue = 5 | pages = 486–9 | year = 1987 | pmid = 3579659}}</ref>
Amitriptyline may be prescribed for other conditions such as [[insomnia]], [[post-traumatic stress disorder]] (PTSD),<ref>National Institute for Clinical Excellence: [http://www.nice.org.uk/nicemedia/pdf/CG026publicinfo.pdf The Treatment of PTSD in Adults and Children]</ref> [[migraine]], [[rebound headache]], [[chronic pain]], [[tinnitus]], [[chronic cough]], [[postherpetic neuralgia]] (persistent pain following a [[shingles]] attack), [[carpal tunnel syndrome]] (CTS), [[fibromyalgia]], [[vulvodynia]], [[interstitial cystitis]], [[UCPPS|male chronic pelvic pain syndrome]], [[irritable bowel syndrome]] (IBS), [[diabetic neuropathy|diabetic peripheral neuropathy]], [[neurological]] pain, and painful [[paresthesia]]s related to [[multiple sclerosis]] and at low doses as a [[prophylaxis]] (preventive) for patients with [[Chronic (medicine)|chronic]] [[migraine]]s.<ref name="pmid3579659">{{cite journal | author = Ziegler D, Hurwitz A, Hassanein R, Kodanaz H, Preskorn S, Mason J | title = Migraine prophylaxis. A comparison of propranolol and amitriptyline | journal = Arch Neurol | volume = 44 | issue = 5 | pages = 486–9 | year = 1987 | pmid = 3579659}}</ref>

Revision as of 21:18, 12 February 2010

Amitriptyline
Clinical data
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • US: WARNING[1]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability30–60% due to first pass metabolism
Protein binding> 90%
MetabolismHepatic
CYP2C19, CYP1A2, CYP2D6
Elimination half-life10–50 hours, with an average of 15 hours
ExcretionRenal
Identifiers
  • 3-(10,11-dihydro- 5H-dibenzoa,dcycloheptene- 5-ylidene)- N,N-dimethyl- 1-propanamine
CAS Number
PubChem CID
DrugBank
ChemSpider
CompTox Dashboard (EPA)
ECHA InfoCard100.000.038 Edit this at Wikidata
Chemical and physical data
FormulaC20H23N
Molar mass277.403 g/mol g·mol−1
3D model (JSmol)
  • c3cc2c(/C(c1c(cccc1)CC2)=C\CCN(C)C)cc3
  (verify)

Amitriptyline (Elavil, Tryptizol, Laroxyl) is a tricyclic antidepressant (TCA).[2]

History

Amitriptyline, under the brand name Elavil, was approved on April 7, 1961 for the treatment of major depression in the United States.[3] It has seen widespread usage throughout the world ever since.

Indications

Approved

Amitriptyline is approved for the treatment of major depression, as well as clinical/endogenous depression and also involutional melancholia or "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 dose initially for elderly or adolescent patients.

Children between the ages of 7 to 10 years typically have 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 three months.[4]

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[5].

Unapproved/Off-label

Amitriptyline may be prescribed for other conditions such as insomnia, post-traumatic stress disorder (PTSD),[6] 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.[7] Typically lower dosages are required for pain modification of 10 to 50 mg daily.[4]

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.[citation needed]

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).[8]

Pharmacology

Amitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the norepinephrine transporter, and moderate effects on the serotonin transporter.[9][10] 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.[10]

Amitriptyline additionally functions as a 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, α1-adrenergic, H1, and mACh receptor antagonist, and σ1 receptor agonist.[11][12][13][14] It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine.[15] 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.[16][17][18]

Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors.[19] 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.[19]

Side effects

Common side effects of using amitriptyline are mostly due to its anticholinergic activity, including: weight gain, dry mouth, changes in appetite, drowsiness, muscle stiffness, nausea, constipation, nervousness, dizziness, blurred vision, urinary retention, insomnia and changes in sexual function. Some rare side effects include tinnitus, hypotension, mania, psychosis, sleep paralysis, hypnagogia, hypnopompia, heart block, arrhythmias, lip and mouth ulcers, extrapyramidal symptoms, depression, and hepatic toxicity.

Overdose

Main article: Tricyclic antidepressant overdose

The symptoms and the treatment of an overdose are largely the same as for the other TCAs.

See also

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ Barbui C, Hotopf M (2001). "Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials". The British Journal of Psychiatry : the Journal of Mental Science. 178: 129–44. PMID 11157426. {{cite journal}}: Unknown parameter |month= ignored (help)
  3. ^ Fangmann P, Assion HJ, Juckel G, González CA, López-Muñoz F (2008). "Half a century of antidepressant drugs: on the clinical introduction of monoamine oxidase inhibitors, tricyclics, and tetracyclics. Part II: tricyclics and tetracyclics". Journal of Clinical Psychopharmacology. 28 (1): 1–4. doi:10.1097/jcp.0b013e3181627b60. PMID 18204333. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ a b British National Formulary 45 (March 2003).
  5. ^ 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.
  6. ^ National Institute for Clinical Excellence: The Treatment of PTSD in Adults and Children
  7. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Otaka M, Jin M, Odashima M; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ http://www.cnsforum.com/content/pictures/imagebank/hirespng/antidep_uptake_specific.png
  10. ^ a b Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 9537821, please use {{cite journal}} with |pmid=9537821 instead.
  11. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 9400006, please use {{cite journal}} with |pmid=9400006 instead.
  12. ^ Alan F. Schatzberg, Charles B. (2006). Essentials of clinical psychopharmacology. American Psychiatric Pub. p. 7. ISBN 1585622435, 9781585622436. {{cite book}}: Check |isbn= value: invalid character (help)
  13. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 11561066, please use {{cite journal}} with |pmid=11561066 instead.
  14. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17689532, please use {{cite journal}} with |pmid=17689532 instead.
  15. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 2568580, please use {{cite journal}} with |pmid=2568580 instead.
  16. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 9435180, please use {{cite journal}} with |pmid=9435180 instead.
  17. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 18048694, please use {{cite journal}} with |pmid=18048694 instead.
  18. ^ Punke MA, Friederich P (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  19. ^ a b Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19549602, please use {{cite journal}} with |pmid=19549602 instead.

Further reading


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