AMITRIPTYLINE PAMOATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H16O6.2C20H23N
Molecular Weight	943.1762
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)CCC=C1C2=CC=CC=C2CCC3=C1C=CC=C3.CN(C)CCC=C4C5=CC=CC=C5CCC6=C4C=CC=C6.OC(=O)C7=CC8=C(C=CC=C8)C(CC9=C%10C=CC=CC%10=CC(C(O)=O)=C9O)=C7O

InChI

InChIKey=HBFZQWHVSYYTGA-UHFFFAOYSA-N

InChI=1S/C23H16O6.2C20H23N/c24-20-16(14-7-3-1-5-12(14)9-18(20)22(26)27)11-17-15-8-4-2-6-13(15)10-19(21(17)25)23(28)29;2*1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h1-10,24-25H,11H2,(H,26,27)(H,28,29);2*3-6,8-12H,7,13-15H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C23H16O6
Molecular Weight	388.3695
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C20H23N
Molecular Weight	277.4033
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 38 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 8146	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 8146	13.3 nM [IC50]
5-hydroxytryptamine receptor 2A 69 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 2737

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 8307	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 8.7393599E11

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

Doses

Dose	Population	Adverse events
100 mg 1 times / day single, intravenous Studied dose Dose: 100 mg, 1 times / day Route: intravenous Route: single Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17512256/	healthy, 21 to 70 years n = 5 Health Status: healthy Age Group: 21 to 70 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/17512256/	Disc. AE: Bradycardia... Other AEs: Agitation, Dry mouth... AEs leading to discontinuation/dose reduction: Bradycardia (grade 3, 20%) Other AEs: Agitation (20%) Dry mouth (20%) Drowsiness (20%) Language disorder (20%) Sources: https://pubmed.ncbi.nlm.nih.gov/17512256/
10 % 1 times / day single, topical Highest studied dose Dose: 10 %, 1 times / day Route: topical Route: single Dose: 10 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21676162/	unhealthy, 57 years n = 1 Health Status: unhealthy Condition: pain Age Group: 57 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/21676162/	Other AEs: Thought disorder, Mental concentration difficult... Other AEs: Thought disorder Mental concentration difficult Sources: https://pubmed.ncbi.nlm.nih.gov/21676162/
520.3 mg 1 times / day single, oral (mean) Studied dose Dose: 520.3 mg, 1 times / day Route: oral Route: single Dose: 520.3 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20923818/	healthy, mean age 22.1 years n = 96 Health Status: healthy Age Group: mean age 22.1 years Sex: M+F Population Size: 96 Sources: https://pubmed.ncbi.nlm.nih.gov/20923818/	Other AEs: Mental status changes... Other AEs: Mental status changes Sources: https://pubmed.ncbi.nlm.nih.gov/20923818/
25 mg 1 times / day multiple, oral Studied dose Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24259978/	unhealthy, mean age 43.2 years n = 16 Health Status: unhealthy Condition: globus pharyngeus Age Group: mean age 43.2 years Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/24259978/	Other AEs: Dry mouth, Sleepiness... Other AEs: Dry mouth (75%) Sleepiness (68.8%) Dizziness (25%) Constipation (18.8%) Palpitations (6.3%) Malaise (6.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/24259978/
75 mg 1 times / day multiple, oral Recommended Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8494126/	unhealthy, mean age 55 years n = 27 Health Status: unhealthy Condition: chronic pain Age Group: mean age 55 years Sex: M+F Population Size: 27 Sources: https://pubmed.ncbi.nlm.nih.gov/8494126/	Disc. AE: Drowsiness, Dry mouth... Other AEs: Drowsiness, Nausea... AEs leading to discontinuation/dose reduction: Drowsiness (10%) Dry mouth (10%) Other AEs: Drowsiness (51.8%) Nausea (7.4%) Headache (7.4%) Dry mouth (63%) Thirst (7.4%) Tiredness (7.4%) Bad taste (18.5%) Attention concentration difficulty (7.4%) Hyperglycaemia (3.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/8494126/
59 mg 1 times / day multiple, oral (mean) Studied dose Dose: 59 mg, 1 times / day Route: oral Route: multiple Dose: 59 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10493324/	unhealthy, mean age 60.4 years n = 25 Health Status: unhealthy Condition: diabetic peripheral neuropathy pain Age Group: mean age 60.4 years Sex: M+F Population Size: 25 Sources: https://pubmed.ncbi.nlm.nih.gov/10493324/	Disc. AE: Ankle edema, Dizziness... Other AEs: Sedation, Dry mouth... AEs leading to discontinuation/dose reduction: Ankle edema (4%) Dizziness (4%) Other AEs: Sedation (32%) Dry mouth (32%) Postural hypotension (20%) Weight gain (24%) Ataxia (8%) Constipation (12%) Lethargy (20%) Edema (8%) Headache (12%) Pruritus (12%) Bad taste (4%) Nausea (4%) Diarrhea (4%) Blurred vision (8%) Sources: https://pubmed.ncbi.nlm.nih.gov/10493324/
520.3 mg 1 times / day single, oral (mean) Studied dose Dose: 520.3 mg, 1 times / day Route: oral Route: single Dose: 520.3 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20923818/	healthy n = 96 Health Status: healthy Sex: M+F Population Size: 96 Sources: https://pubmed.ncbi.nlm.nih.gov/20923818/	Other AEs: Tachycardia... Other AEs: Tachycardia Sources: https://pubmed.ncbi.nlm.nih.gov/20923818/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670 inhibitor 1532	substrate 985	substrate 1168 inhibitor 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1410 CYP2C8 869 OCT1 498 OCT2 630	CYP1A2 1013 CYP2C19 955 CYP2B6 648 UGT2B10 127 UGT1A4 345

Drug as perpetrator

Target	Modality	Activity
OCT2 631	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/	yes [IC50 14 uM]
OCT1 513	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/20567254/	yes [IC50 6.99 uM]
CYP3A4 1857	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16415122/	yes [IC50 8.8 uM]
CYP2C8 923	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2015019/	yes [Inhibition 200 uM]
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12228186/	yes [Ki 31 uM]
CYP2C19 1484	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12228186/	yes [Ki 37.7 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1013	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042727/	no
CYP2C19 955	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042727/	no
CYP2B6 648	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11259560/	yes
CYP2C9 985	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042727/	yes
CYP2D6 1168	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042727/	yes
CYP3A4 1670	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042727/	yes
UGT1A4 345	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	yes
UGT2B10 127	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 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
MolPort	MolPort-001-662-651	https://www.molport.com/shop/molecule-link/MolPort-001-662-651
ZINC	ZINC000000968257	http://zinc15.docking.org/substances/ZINC000000968257
eMolecules	739635	https://www.emolecules.com/cgi-bin/more?vid=739635

PubMed

Title	Date	PubMed
Inhibition of HIV replication by neuroleptic agents and their potential use in HIV infected patients with AIDS related dementia.	2000 Apr	10773489
Syncope associated with concurrent amitriptyline and fluconazole therapy.	2000 Dec	11144697
[Extrapyramidal reactions after epidural droperidol].	2000 Oct	11075569
Amitriptyline and somnambulism.	2000 Oct	11054994
Long-term effects of tricyclic antidepressants on norepinephrine kinetics in humans.	2001	11341486
The concentration of three anti-seizure medications in hair: the effects of hair color, controlling for dose and age.	2001	11339881
Dopaminergic activity in transgenic mice underexpressing glucocorticoid receptors: effect of antidepressants.	2001	11226678
Evidence for the use of gabapentin in the treatment of diabetic peripheral neuropathy.	2001 Apr	11354388
Noradrenergic dysfunction and antidepressant treatment response.	2001 Apr	11313162
Postherpetic neuralgia. Treatment with amitriptyline is cheaper than with aciclovir.	2001 Apr 7	11290647
Review of pharmacokinetic and pharmacodynamic interaction studies with citalopram.	2001 Aug	11532381
Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine.	2001 Aug	11511404
Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients.	2001 Aug	11477329
Cromolyn cream for recalcitrant idiopathic vulvar vestibulitis: results of a placebo controlled study.	2001 Feb	11158692
Amitriptyline: still efficacious, but at what cost?	2001 Feb	11157421
Serum levels of amitriptyline and therapeutic effect in non-delusional moderately to severely depressed in-patients: a therapeutic window relationship.	2001 Jan	11229620
Amitriptyline enhances the central component of physiological tremor.	2001 Jan	11118252
Mirtazepine: heir apparent to amitriptyline?	2001 Jan-Feb	11406877
Late-onset GM2 gangliosidosis presenting as burning dysesthesias.	2001 Jul	11483398
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
Patterns of response to repeated total sleep deprivations in depression.	2001 May	11313092
Drug use and five-year incidence of age-related cataracts: The Beaver Dam Eye Study.	2001 Sep	11535471

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.

Substance Class	Chemical Created by `admin` on `Sat Dec 17 00:08:29 UTC 2022` Edited by `admin` on `Sat Dec 17 00:08:29 UTC 2022`
Record UNII	YX6VNM127F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMITRIPTYLINE PAMOATE

Common Name

English

2-NAPHTHALENECARBOXYLIC ACID, 4,4'-METHYLENEBIS(3-HYDROXY-, COMPD. WITH 3-(10,11-DIHYDRO-5H-DIBENZO(A,D)CYCLOHEPTEN-5-YLIDENE)-N,N-DIMETHYL-1-PROPANAMINE) (1:2)

Common Name

English

2-NAPHTHOIC ACID, 4,4'-METHYLENEBIS(3-HYDROXY-, COMPD. WITH 10,11-DIHYDRO-N,N-DIMETHYL-5H-DIBENZO(A,D)CYCLOHEPTENE-.DELTA.5,.GAMMA.-PROPYLAMINE) (1:2)

Common Name

English

1-PROPANAMINE, 3-(10,11-DIHYDRO-5H-DIBENZO(A,D)CYCLOHEPTEN-5-YLIDENE)-N,N-DIMETHYL-, 4,4'-METHYLENEBIS(3-HYDROXY-2-NAPHTHALENECARBOXYLATE)(2:1)

Common Name

English

Amitriptyline pamoate [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C94727