AMITRIPTYLINE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H23N.ClH
Molecular Weight	313.864
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of AMITRIPTYLINE HYDROCHLORIDE

Structure Search

SMILES

Cl.CN(C)CCC=C1C2=CC=CC=C2CCC3=CC=CC=C13

InChI

InChIKey=KFYRPLNVJVHZGT-UHFFFAOYSA-N

InChI=1S/C20H23N.ClH/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;1H

HIDE SMILES / InChI

Description
Sources: http://www.emedexpert.com/facts/amitriptyline-facts.shtml
Curator's Comment: description was created based on several sources, including http://www.rxlist.com/elavil-drug.htm https://www.ncbi.nlm.nih.gov/pubmed/23235671; https://www.ncbi.nlm.nih.gov/pubmed/11157426; http://www.ncbi.nlm.nih.gov/pubmed/16871467; http://www.ncbi.nlm.nih.gov/pubmed/2578912; http://www.ncbi.nlm.nih.gov/pubmed/?term=15943846

Amitriptyline is a derivative of dibenzocycloheptadiene and a tricyclic antidepressant (TCA) and is mainly used to treat symptoms of depression. It works on the central nervous system (CNS) by inhibiting the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Amitriptyline has been frequently used as an active comparator in clinical trials on newer antidepressants. It is rarely used as a first-line antidepressant nowadays due to its high degree of toxicity in overdose and generally poorer tolerability than the newer antidepressants.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sodium-dependent noradrenaline transporter 39 Target ID: P23975 Gene ID: 6530.0 Gene Symbol: SLC6A2 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/14744476	Inhibitor 8504	3.45 nM [IC50]
Sodium-dependent serotonin transporter 41 Target ID: P31645 Gene ID: 6532.0 Gene Symbol: SLC6A4 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/14744476	Inhibitor 8504	13.3 nM [IC50]
5-hydroxytryptamine receptor 2A 73 Target ID: P28223 Gene ID: 3356.0 Gene Symbol: HTR2A Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/7855217	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depressive disorder 4 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1e6d2c80-fbc8-444e-bdd3-6a91fe1b95bd	Preventing		Approved 8583	AMITRIPTYLINE HYDROCHLORIDE Approved Use For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states. Launch Date 1997

C_max

Value	Dose	Co-administered	Analyte	Population
15.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10383563	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		AMITRIPTYLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
593 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10383563	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		AMITRIPTYLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
20.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10383563	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		AMITRIPTYLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
7.7% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6125396	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:		AMITRIPTYLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	substrate 1193	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP2C8 1057 OCT1 620 OCT2 779	CYP1A2 1197 CYP2C19 1119 CYP2B6 776 UGT2B10 131 UGT1A4 399

Drug as perpetrator

Target	Modality	Activity
OCT2 782	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/	yes [IC50 14 uM]
OCT1 656	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20567254/	yes [IC50 6.99 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16415122/	yes [IC50 8.8 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2015019/	yes [Inhibition 200 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12228186/	yes [Ki 31 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12228186/	yes [Ki 37.7 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042727/	no
CYP2C19 1119	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042727/	no
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11259560/	yes
CYP2C9 1193	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042727/	yes
CYP2D6 1388	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042727/	yes
CYP3A4 1946	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042727/	yes
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	yes
UGT2B10 131	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571977/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2666	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2666
eMolecules	739635	https://www.emolecules.com/cgi-bin/more?vid=739635
MolPort	MolPort-001-662-651	https://www.molport.com/shop/molecule-link/MolPort-001-662-651
ZINC	ZINC000000968257	http://zinc15.docking.org/substances/ZINC000000968257

PubMed

Title	Date	PubMed
[Cardiac arrest following amitriptylin and adrenaline].	1975 Jun 16	1145841
[Individual conditions of pharmacogenic confusion conditions. Comparison of amitriptyline and clozapine].	1976	1019368
Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding.	1999 Aug	10379421
Case report: adverse effects of taking tricyclic antidepressants and smoking marijuana.	1999 Nov	10587776
[Hypotension refractory to ephedrine after sympathetic blockade in a patient on long-term therapy with tricyclic antidepressants].	1999 Oct	10563144
Antidepressants upregulate messenger RNA levels of the neuroprotective enzyme superoxide dismutase (SOD1).	2000 Jan	10721683
Gender differences in depression associated with neurologic illness: clinical correlates and pharmacologic response.	2001	11480103
A randomized trial of fluoxetine versus amitriptyline in musculo-skeletal pain.	2001	11475920
Tianeptine: a review of its use in depressive disorders.	2001	11463130
Hyposecretion of the adrenal androgen dehydroepiandrosterone sulfate and its relation to clinical variables in inflammatory arthritis.	2001	11299059
Evidence for the use of gabapentin in the treatment of diabetic peripheral neuropathy.	2001 Apr	11354388
The effects of amitriptyline, citalopram and reboxetine on autonomic nervous system. A randomised placebo-controlled study on healthy volunteers.	2001 Apr	11349386
Noradrenergic dysfunction and antidepressant treatment response.	2001 Apr	11313162
Antidepressive treatment with amitriptyline and paroxetine: comparable effects on heart rate variability.	2001 Apr	11270923
Changes in quantitatively assessed tremor during treatment of major depression with lithium augmented by paroxetine or amitriptyline.	2001 Apr	11270916
Combined pharmacotherapy for nocturnal enuresis.	2001 Aug	11519898
Interaction of psychotropic drugs with monoamine oxidase in rat brain.	2001 Aug	11518022
Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine.	2001 Aug	11511404
Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates.	2001 Aug	11505218
Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients.	2001 Aug	11477329
Regional potassium distribution in the brain in forensic relevant types of intoxication preliminary morphometric evaluation using a histochemical method.	2001 Feb	11307856
Preventive therapy in pediatric migraine.	2001 Feb	11292228
Amitriptyline treatment in chronic drug-induced headache: a double-blind comparative pilot study.	2001 Feb	11251703
Gabapentin for the treatment of tinnitus: a case report.	2001 Feb	11233342
Prolonged coma and loss of brainstem reflexes following amitriptyline overdose.	2001 Feb	11205078
Cromolyn cream for recalcitrant idiopathic vulvar vestibulitis: results of a placebo controlled study.	2001 Feb	11158692
Salmon calcitonin potentiates the analgesia induced by antidepressants.	2001 Jan	11274717
[Non-fatal effect of highly toxic amitriptyline level after suicide attempt. A case report].	2001 Jan	11221556
Weight outcomes among antidepressant users in nursing facilities.	2001 Jan	11207842
Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome.	2001 Jan	11204086
The effects of antidepressants on obstructed and unobstructed gait in healthy elderly people.	2001 Jan	11193231
Lamotrigine for central poststroke pain: a randomized controlled trial.	2001 Jan 23	11160953
Mirtazepine: heir apparent to amitriptyline?	2001 Jan-Feb	11406877
Antinociception by tricyclic antidepressants in the rat formalin test: differential effects on different behaviours following systemic and spinal administration.	2001 Jul	11406338
Efficacy of amitriptyline as a pharmacological adjunct to behavioral modification in the management of aggressive behaviors in dogs.	2001 Jul-Aug	11450832
Acute eosinophilic pneumonia associated with amitriptyline in a hemodialysis patient.	2001 Jun	11456405
Involvement of adenosine in the effect of antidepressants on glutamate and aspartate release in the rat prefrontal cortex.	2001 Jun	11414661
In vitro reaction of formaldehyde with fenfluramine: conversion to N-methyl fenfluramine.	2001 Mar	11300512
Discovery of a novel member of the histamine receptor family.	2001 Mar	11179435
[Comparative studies of adverse effects in patients with refractory depression treated with amitryptyline, mianserin and unilateral ECT].	2001 Mar-Apr	11490887
Bipolar disorder after mefloquine treatment.	2001 May	11394195
Treatment of neuropathic pain with venlafaxine.	2001 May	11346061
Inhibition of synovial plasma extravasation by preemptive administration of an antiinflammatory irrigation solution in the rat knee.	2001 May	11323366
Patterns of response to repeated total sleep deprivations in depression.	2001 May	11313092
Combining psychotherapy and antidepressants in the treatment of depression.	2001 May	11313088
[St. John's wort: a pharmaceutical with potentially dangerous interactions].	2001 May 10	11407242
Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.	2001 Oct	11561066
Efficacy of spinal manipulation for chronic headache: a systematic review.	2001 Sep	11562654
HPLC of basic drugs on microparticulate strong cation-exchange materials - a review.	2001 Sep 15	11516893
Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care.	2001 Sep 22	11566831

Patents

Sample Use Guides

In Vivo Use Guide

For outpatients, 75 mg of amitriptyline HCl a day in divided doses. If necessary, this may be increased to a total of 150 mg per day. An alternate method of initiating therapy in outpatients is to begin with 50 to 100 mg amitriptyline HCl at bedtime. This may be increased by 25 or 50 mg as necessary in the bedtime dose to a total of 150 mg per day. Hospitalized patients may require 100 mg a day initially. This can be increased gradually to 200 mg a day if necessary up to 300 mg a day. Not recommended for patients under 12 years of age

Route of Administration: Oral

In Vitro Use Guide

Amitriptyline was used at 40 uM in isolated rat hepatocytes for 60,120,180 min.

Name

Type

Language

AMITRIPTYLINE HYDROCHLORIDE

Common Name

English

ETRAFON-A COMPONENT AMITRIPTYLINE HYDROCHLORIDE

Preferred Name

English

AMITRIPTYLINE HYDROCHLORIDE [MI]

Common Name

English

LIMBITROL DS COMPONENT AMITRIPTYLINE HYDROCHLORIDE

Common Name

English

LIMBITROL COMPONENT AMITRIPTYLINE HYDROCHLORIDE

Common Name

English

NSC-104210

Code

English

AMITRIPTYLINE HYDROCHLORIDE [MART.]

Common Name

English

AMITRIPTYLINI HYDROCHLORIDUM [WHO-IP LATIN]

Common Name

English

SYNEUDON

Common Name

English

Amitriptyline hydrochloride [WHO-DD]

Common Name

English

ENDEP

Brand Name

English

AMITID

Brand Name

English

AMITRIPTYLINE HYDROCHLORIDE [WHO-IP]

Common Name

English

NOVOPROTECT

Common Name

English

ELAVIL

Brand Name

English

ETRAVIL

Brand Name

English

AMITRIPTYLINE HYDROCHLORIDE [USP IMPURITY]

Common Name

English

AMITRIL

Brand Name

English

AMITRIPTYLINE HYDROCHLORIDE [EP IMPURITY]

Common Name

English

AMITRIPTYLINE HYDROCHLORIDE [VANDF]

Common Name

English

AMITRIPTYLINE HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

NIH 10794

Code

English

AMITRIPTYLINE HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

AMITRIPTYLINE HCL

Common Name

English

AMITRIPTYLINE HYDROCHLORIDE [JAN]

Common Name

English

AMITRIPTYLINE HYDROCHLORIDE [USP-RS]

Common Name

English

1-PROPANAMINE, 3-(10,11-DIHYDRO-5H-DIBENZO(A,D)CYCLOHEPTEN-5-YLIDENE)-N,N-DIMETHYL-, HYDROCHLORIDE

Systematic Name

English

AMITRIPTYLINE HYDROCHLORIDE [HSDB]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C94727