U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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

SMILES

Cl.CN(C)CCC=C1C2=C(CCC3=C1C=CC=C3)C=CC=C2

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
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

1961
146
Targets

Targets

Primary TargetPharmacologyConditionPotency
Sodium-dependent noradrenaline transporter
38
Target ID: P23975
Gene ID: 6530.0
Gene Symbol: SLC6A2
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 3.45 nM [IC50]
Sodium-dependent serotonin transporter
40
Target ID: P31645
Gene ID: 6532.0
Gene Symbol: SLC6A4
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 13.3 nM [IC50]
5-hydroxytryptamine receptor 2A
69
Target ID: P28223
Gene ID: 3356.0
Gene Symbol: HTR2A
Target Organism: Homo sapiens (Human)
Antagonist
2778
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
Approved
8429
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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

AEs

AESignificanceDosePopulation
Agitation 20%
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/
Drowsiness 20%
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/
Dry mouth 20%
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/
Language disorder 20%
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/
Bradycardia grade 3, 20%
Disc. AE
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/
Mental concentration difficult
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/
Thought disorder
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/
Mental status changes
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/
Constipation 18.8%
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/
Dizziness 25%
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/
Malaise 6.3%
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/
Palpitations 6.3%
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/
Sleepiness 68.8%
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/
Dry mouth 75%
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/
Drowsiness 10%
Disc. AE
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/
Dry mouth 10%
Disc. AE
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/
Bad taste 18.5%
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/
Hyperglycaemia 3.7%
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/
Drowsiness 51.8%
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/
Dry mouth 63%
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/
Attention concentration difficulty 7.4%
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/
Headache 7.4%
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/
Nausea 7.4%
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/
Thirst 7.4%
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/
Tiredness 7.4%
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/
Constipation 12%
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/
Headache 12%
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/
Pruritus 12%
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/
Lethargy 20%
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/
Postural hypotension 20%
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/
Weight gain 24%
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/
Dry mouth 32%
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/
Sedation 32%
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/
Bad taste 4%
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/
Diarrhea 4%
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/
Nausea 4%
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/
Ankle edema 4%
Disc. AE
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/
Dizziness 4%
Disc. AE
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/
Ataxia 8%
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/
Blurred vision 8%
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/
Edema 8%
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/
Tachycardia
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/
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587
substrate
1037
substrate
1217

inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP2C19
1478

CYP2C8
911

OCT1
512

OCT2
647
CYP1A2
1054

CYP2C19
991

CYP2B6
664

UGT2B10
127

UGT1A4
347
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OCT2
648
 yes [IC50 14 uM]
OCT1
543
 yes [IC50 6.99 uM]
CYP3A4
1925
 yes [IC50 8.8 uM]
CYP2C8
965
 yes [Inhibition 200 uM]
CYP2D6
1891
 yes [Ki 31 uM]
CYP2C19
1553
 yes [Ki 37.7 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1054
 no
CYP2C19
991
 no
CYP2B6
664
 yes
CYP2C9
1037
 yes
CYP2D6
1217
 yes
CYP3A4
1737
 yes
UGT1A4
347
 yes
UGT2B10
127
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
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

PubMed

TitleDatePubMed
[Cardiac arrest following amitriptylin and adrenaline].
1975 Jun 16
[Individual conditions of pharmacogenic confusion conditions. Comparison of amitriptyline and clozapine].
1976
Case report: adverse effects of taking tricyclic antidepressants and smoking marijuana.
1999 Nov
[Hypotension refractory to ephedrine after sympathetic blockade in a patient on long-term therapy with tricyclic antidepressants].
1999 Oct
Inhibition of HIV replication by neuroleptic agents and their potential use in HIV infected patients with AIDS related dementia.
2000 Apr
Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption.
2000 Apr
Syncope associated with concurrent amitriptyline and fluconazole therapy.
2000 Dec
Antidepressants upregulate messenger RNA levels of the neuroprotective enzyme superoxide dismutase (SOD1).
2000 Jan
Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds.
2000 Jul 28
Prolonged QT interval and torsades de pointes caused by the combination of fluconazole and amitriptyline.
2000 Mar
Amitriptyline and somnambulism.
2000 Oct
Activation of cytochrome P450 gene expression in the rat brain by phenobarbital-like inducers.
2000 Sep
Gender differences in depression associated with neurologic illness: clinical correlates and pharmacologic response.
2001
Long-term effects of tricyclic antidepressants on norepinephrine kinetics in humans.
2001
The concentration of three anti-seizure medications in hair: the effects of hair color, controlling for dose and age.
2001
Hyposecretion of the adrenal androgen dehydroepiandrosterone sulfate and its relation to clinical variables in inflammatory arthritis.
2001
Amitriptyline versus bupivacaine in rat sciatic nerve blockade.
2001 Apr
Antidepressive treatment with amitriptyline and paroxetine: comparable effects on heart rate variability.
2001 Apr
Changes in quantitatively assessed tremor during treatment of major depression with lithium augmented by paroxetine or amitriptyline.
2001 Apr
Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate.
2001 Apr
[Sensory neuropathy in HIV infection: pathogenesis and therapy].
2001 Apr 14
Regional potassium distribution in the brain in forensic relevant types of intoxication preliminary morphometric evaluation using a histochemical method.
2001 Feb
Preventive therapy in pediatric migraine.
2001 Feb
Transplacental transfer of amitriptyline and nortriptyline in isolated perfused human placenta.
2001 Feb
Gabapentin for the treatment of tinnitus: a case report.
2001 Feb
Amitriptyline: still efficacious, but at what cost?
2001 Feb
The effect of polyelectrolyte counterion specificity, charge density, and conformation on polyelectrolyte-amphiphile interaction: the carrageenan/furcellaran-amitriptyline system.
2001 Feb
Serum levels of amitriptyline and therapeutic effect in non-delusional moderately to severely depressed in-patients: a therapeutic window relationship.
2001 Jan
Weight outcomes among antidepressant users in nursing facilities.
2001 Jan
Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome.
2001 Jan
The effects of antidepressants on obstructed and unobstructed gait in healthy elderly people.
2001 Jan
Mirtazepine: heir apparent to amitriptyline?
2001 Jan-Feb
Cyclobenzaprine and back pain: a meta-analysis.
2001 Jul 9
Assessment of DNA damage in C6 glioma cells after antidepressant treatment using an alkaline comet assay.
2001 Jun
Retro-orbital tumour--an uncommon cause of headache in pregnancy.
2001 Jun
Pharmacological modulation of SK3 channels.
2001 Jun
In vitro reaction of formaldehyde with fenfluramine: conversion to N-methyl fenfluramine.
2001 Mar
Effects of amitriptyline on diurnal variations of oxidation-reduction enzyme activities in rat lymphocytes during experimental desynchronosis.
2001 May
Treatment of neuropathic pain with venlafaxine.
2001 May
Advances in the management of neuropathic pain.
2001 May
High-performance liquid chromatographic method combining radiochemical and ultraviolet detection for determination of low activities of uridine 5'-diphosphate-glucuronosyltransferase.
2001 May 15
Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.
2001 Oct
Efficacy of spinal manipulation for chronic headache: a systematic review.
2001 Sep
Drug use and five-year incidence of age-related cataracts: The Beaver Dam Eye Study.
2001 Sep
Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care.
2001 Sep 22
Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels.
2007 May
Patents

Patents

JP2007512339A
43
JP2007525670A
148
JP2011528275A
455
JP4653399B2
50
JPS5569567A
7

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
EP   HSDB   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
Common Name English
AMITRIPTYLINE HYDROCHLORIDE [MI]
Common Name English
LIMBITROL DS COMPONENT AMITRIPTYLINE HYDROCHLORIDE
Common Name English
AMITRIPTYLINE HYDROCHLORIDE COMPONENT OF LIMBITROL DS
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 COMPONENT OF LIMBITROL
Common 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
ETRAFON-A COMPONENT AMITRIPTYLINE HYDROCHLORIDE
Common Name English
AMITRIPTYLINE HYDROCHLORIDE [VANDF]
Common Name English
AMITRIPTYLINE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
AMITRIPTYLINE HYDROCHLORIDE COMPONENT OF ETRAFON-A
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
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
Code System Code Type Description
RS_ITEM_NUM
1029002
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
CAS
549-18-8
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
DAILYMED
26LUD4JO9K
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
AMITRIPTYLINE HYDROCHLORIDE
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY Description: Colourless crystals or a white or almost white powder; odourless or almost odourless. Solubility: Soluble in 1 part of water and in 1.5 parts of ethanol (~750 g/l) TS; practically insoluble in ether R. Category: Antidepressant. Storage: Amitriptyline hydrochloride should be kept in a tightly closed container, protected from light. Additional information: Amitriptyline hydrochloride has a bitter and burning taste that is followed by a sensation of numbness. Even in the absence of light, Amitriptyline hydrochloride is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures. Definition: Amitriptyline hydrochloride contains not less than 99.0% and not more than 101.5% of C20H23N,HCl, calculated with reference to the dried substance.
SMS_ID
100000090311
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
ECHA (EC/EINECS)
208-964-6
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
PUBCHEM
11065
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
FDA UNII
26LUD4JO9K
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
DRUG BANK
DBSALT000009
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
MERCK INDEX
m1753
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY Merck Index
NSC
104210
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
ChEMBL
CHEMBL629
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
EVMPD
SUB00474MIG
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
NCI_THESAURUS
C28819
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
RXCUI
203168
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY RxNorm
EPA CompTox
DTXSID9033187
Created by admin on Fri Dec 15 15:39:04 GMT 2023 , Edited by admin on Fri Dec 15 15:39:04 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of AMITRIPTYLINE
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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