PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
amitriptyline

2D structure

Overview

Generic Names: Amitriprolidine; Amitriptylin; Amitriptyline HCL; Amitriptyline Hydrochloride; Amitryptiline; Amitryptyline; Amytriptiline
Trade Names: Adepress; Adepril; Amitid; Amitril; Damilan; Damilen; Elanil; Elavil; Endep; Flavyl; Hexathane; Horizon; Lantron; Laroxil; Laroxyl; Lentizol; Proheptadiene; Redomex; Saroten; Sarotex; Seroten; Sylvemid; Triptanol; Triptilin; Triptisol; Tryptanol; Tryptizol; dAmitriptyline
Brand Mixtures: Apo Peram Tab 2-25 (Amitriptyline Hydrochloride + Perphenazine); Apo Peram Tab 3-15 (Amitriptyline Hydrochloride + Perphenazine); Elavil Plus Tab (Amitriptyline Hydrochloride + Perphenazine); Etrafon 2 10 (Amitriptyline Hydrochloride + Perphenazine); Etrafon D Tab (Amitriptyline Hydrochloride + Perphenazine); Etrafon F Tab (Amitriptyline Hydrochloride + Perphenazine); Etrafon a Tab (Amitriptyline Hydrochloride + Perphenazine); Pms-Levazine 2/25 Tab (Amitriptyline Hydrochloride + Perphenazine); Pms-Levazine 3/15 Tab (Amitriptyline Hydrochloride + Perphenazine); Pms-Levazine 4/25 Tab (Amitriptyline Hydrochloride + Perphenazine); Proavil Tab (Amitriptyline Hydrochloride + Perphenazine); Triavil Tab (Amitriptyline Hydrochloride + Perphenazine)
PharmGKB Accession Id: PA448385

Description

Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines. PubChem (source: Drug Bank)

Indication

For the treatment of anxiety, bipolar disorders, and depression. (source: Drug Bank)

ATC Therapeutic Category

  • N06AA:Non-selective monoamine reuptake inhibitors

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Amitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline. (source: Drug Bank)

Pharmacology

Amitriptyline, a tertiary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. It is extremely sedating, and thus improvement of sleep patterns can be the first benefit of treatment. Amitriptyline exhibits strong anticholinergic activity, cardiovascular effects including orthostatic hypotension, changes in heart rhythm and conduction, and a lowering of the seizure threshold. As with other antidepressants, several weeks of therapy may be required in order to realize the full clinical benefit of amitriptyline. Although not a labelled indication, amitriptyline is widely used in the management of chronic nonmalignant pain (e.g., post-herpetic neuralgia, fibromyalgia). (source: Drug Bank)

Food Interactions

Avoid St.John's Wort.
Avoid alcohol.
Avoid excessive quantities of coffee or tea (Caffeine).
Take with food to reduce irritation. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Exclusively hepatic, with first pass effect. Amitriptyline is demethylated in the liver to its primary active metabolite, nortriptyline. (source: Drug Bank)

Protein Binding

Very highly protein bound (90% or more) in plasma and tissues (source: Drug Bank)

Absorption

Rapidly and well absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). (source: Drug Bank)

Toxicity

LD<sub>50</sub>=350 mg/kg (in mice). Symptoms of overdose include abnormally low blood pressure, confusion, convulsions, dilated pupils and other eye problems, disturbed concentration, drowsiness, hallucinations, impaired heart function, rapid or irregular heartbeat, reduced body temperature, stupor, and unresponsiveness or coma. (source: Drug Bank)

Isomeric SMILES Code:

CN(C)CCC=C1c2ccccc2CCc3c1cccc3 (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs4148740 at chr7:86990039 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  2. rs10280101 at chr7:86991521 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  3. rs7787082 at chr7:86994987 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  4. rs2032583 at chr7:86998497 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  5. rs4148739 at chr7:86998985 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  6. rs11983225 at chr7:86999456 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  7. rs10248420 at chr7:87002922 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  8. rs2235040 at chr7:87003686 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  9. rs12720067 at chr7:87007292 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  10. rs2235015 at chr7:87037500 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  11. rs11188072 at chr10:96509051 in CYP2C19
    This promoter variant is part of CYP2C19*17 haplotype, which causes increased acitivity and increased transcription of CYP2C19. Patients carrying this allele may exhibit a lack of response to commonly prescribed dosages of certain proton pump inhibitors (PPIs) and antidepressants, due to ultrarapid clearance of these drugs. CYP2C19*17 carriers are more likely to benifit from tamoxifen treatment.
    Variant Name:
    CYP2C19: -3402C>T
    Related Drugs:
    amitriptyline, citalopram, clomipramine, escitalopram, omeprazole, proguanil, tamoxifen
    Evidence:
    PMID:16413245
    PMID:17625515
    PMID:18294333
  12. rs12248560 at chr10:96511647 in CYP2C19
    This promoter variant is part of CYP2C19*17 haplotype, which causes increased acitivity and increased transcription of CYP2C19. Patients carrying this allele may exhibit a lack of response to commonly prescribed dosages of certain proton pump inhibitors (PPIs) and antidepressants, due to ultrarapid clearance of these drugs. CYP2C19*17 carriers are more likely to benifit from tamoxifen treatment.
    Variant Name:
    CYP2C19: -806C>T
    Related Drugs:
    amitriptyline, citalopram, clomipramine, escitalopram, omeprazole, proguanil, tamoxifen
    Evidence:
    PMID:16413245
    PMID:18024866
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
  •   
  •   
  • PK
  • FA
  •   
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C19
  • CO
  •   
  • PK
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  • CO
  •   
  • PK
  •   
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP2E1
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
SLC22A1
  •   
  •   
  •   
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
SLC6A4
  • CO
  •   
  •   
  •   
  • GN
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
ADRA2A Uncurated Annotation (source: Drug Bank)
KCNQ2 Uncurated Annotation (source: Drug Bank)
SLC6A2 Uncurated Annotation (source: Drug Bank)
SLC6A4 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
lidocaine
  • CO
  •   
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
phenytoin
  • CO
  •   
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  •   
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
altretamine Uncurated Annotation Risk of severe hypotension (source: Drug Bank)
atazanavir Uncurated Annotation Atazanavir increases the effect and toxicity of tricyclics (source: Drug Bank)
carbamazepine Uncurated Annotation The tricyclics increases the effect of carbamazepine (source: Drug Bank)
cimetidine Uncurated Annotation Cimetidine increases the effect of tricyclic agent (source: Drug Bank)
cisapride Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clonidine Uncurated Annotation The tricyclic decreases the effect of clonidine (source: Drug Bank)
dobutamine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
donepezil Uncurated Annotation Possible antagonism of action (source: Drug Bank)
dopamine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
duloxetine Uncurated Annotation Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank)
ephedra Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
ephedrine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
epinephrine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
fenoterol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
fluconazole Uncurated Annotation The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank)
fluoxetine Uncurated Annotation Fluoxetine increases the effect and toxicity of tricyclics (source: Drug Bank)
fluvoxamine Uncurated Annotation Fluvoxamine increases the effect and toxicity of tricyclics (source: Drug Bank)
galantamine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
grepafloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
guanethidine Uncurated Annotation The tricyclic decreases the effect of guanethidine (source: Drug Bank)
isocarboxazid Uncurated Annotation Possibility of severe adverse effects (source: Drug Bank)
isoproterenol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
ketoconazole Uncurated Annotation The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank)
mephentermine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
mesoridazine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
metaraminol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
methoxamine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
moclobemide Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
norepinephrine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
orciprenaline Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
phenelzine Uncurated Annotation Possibility of severe adverse effects (source: Drug Bank)
phenylephrine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
phenylpropanolamine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
pirbuterol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
procaterol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
pseudoephedrine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
quinidine Uncurated Annotation Quinidine increases the effect of tricyclic agent (source: Drug Bank)
quinidine Uncurated Annotation Quinidine increases the effect of tricyclic agent (source: Drug Bank)
rasagiline Uncurated Annotation Possibility of severe adverse effects (source: Drug Bank)
rifabutin Uncurated Annotation The rifamycin decreases the effect of tricyclics (source: Drug Bank)
rifampin Uncurated Annotation The rifamycin decreases the effect of tricyclics (source: Drug Bank)
ritonavir Uncurated Annotation Ritonavir increases the effect and toxicity of tricyclics (source: Drug Bank)
rivastigmine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
salbutamol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
sibutramine Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
sparfloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
terbutaline Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
terfenadine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
thioridazine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
tranylcypromine Uncurated Annotation Possibility of severe adverse effects (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
Phenotype data available No genotype data Literature annotations available Not annotated
Depression
  • CO
  •   
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Depression, Postpartum
  • CO
  •   
  •   
  •   
  • GN
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Curated Phenotype Datasets

These datasets are sorted alphabetically by title.

  1. Drug-Induced Long QT Intervals
    • Genotype data available
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • PD
    Submitted by Dan Roden, MD involving ADRB1, ADRB2, KCNE1, KCNE2, KCNH2, KCNQ1, SCN5A, almokalant, amiodarone, amitriptyline, bretylium, bupivacaine, cisapride, disopyramide, dofetilide, encainide, fluconazole, haloperidol, hydroquinidine, isoflurane, itraconazole, ketoconazole, lithium, loratadine, metoclopramide, nortriptyline, procainamide, quinidine, sematilide, sotalol, sulfamethoxazole, thioridazine, trimethoprim, , Long QT Syndrome, Proarrhythmia and Torsades de Pointes

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. Genetic Variants in Tricyclic Antidepressant associated Adverse Events
  2. Physicochemical determinants of human renal clearance
  3. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

Downloads

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LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00321
ChEBI ID:
2666
KEGG Compound ID:
C06824
PubChem Compound ID:
2160
PubChem Substance ID:
9042
IUPHAR Ligand ID:
200

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

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