QuickView for Amitriptyline (compound)

Summary
General Info

PubChem

PubChem Compound 11065

Name:	Amitriptyline
PubChem Compound ID:	11065
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.
Molecular formula:	C₂₀H₂₄ClN
Molecular weight:	313.864 g/mol
Synonyms:	Elavil (TN); Levate; EU-0100112; Proheptadien monohydrochloride; Daprimen; 5-(3-Dimethylaminopropylidene)dibenzo(a,d)(1,4)cycloheptadiene hydrochloride; Tryptizol; Tryptanol; NIH 10794; Trepiline. show more » Elavil (TN); Levate; EU-0100112; Proheptadien monohydrochloride; Daprimen; 5-(3-Dimethylaminopropylidene)dibenzo(a,d)(1,4)cycloheptadiene hydrochloride; Tryptizol; Tryptanol; NIH 10794; Trepiline; 5-(3-Dimethylaminopropylidene)dibenzo[a,d][1,4]cycloheptadiene hydrochloride; DRG-0169; Novotriptyn; Domical; Amyzol; Triavil; Teperin; Amitrip; 8058-15-9; 50-48-6; Pinsaun; Amitriptyline hydrochloride; Damilen hydrochloride; NCGC00024433-03; 5H-Dibenzo[a,d]cycloheptene-Delta(sup5),gamma-propylamine, 10,11-dihydro-N,N-dimethyl-, hydrochloride; 1-Propanamine, 3-(10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5-ylidene)-N,N-dimethyl-, hydrochloride; Amitril; Amiplin; Saroten Retard; Endep; NSC 104210; Larozyl; MLS000028437; EINECS 208-964-6; Tridep; 5H-Dibenzo(a,d)cycloheptene-delta(sup 5),gamma-propylamine, 10,11-dihydro-N,N-dimethyl-, hydrochloride; Etravil; Amyline; Amilent; SMR000058368; Amavil; Oasil-M; Miketorin; Novoprotect; Rantoron; Elavil; Uxen; Trynol; 5H-Dibenzo[a,d]cycloheptene-Delta5,gamma-propylamine, 10,11-dihydro-N,N-dimethyl-, hydrochloride (6CI,8CI); ADT-Zimaia; Amicen; Euplit; Lentizol; Yamanouchi; Sarotena; Tryptacap hydrochloride; 5H-Dibenzo(a,d)cycloheptene-delta5,gamma-propylamine, 10,11-dihydro-N,N-dimethyl-, hydrochloride (8CI); Deprex; Amitriptyline hydrochloride [JAN]; Sylvemid; Tryptizol retard; Amitriptyline hydrochloride (JP15/USP); Kyliran; Syneudon; Maxivalet; Amitryptiline hydrochloride; 10,11-Dihydro-N,N-dimethyl-5H-dibenzo(a,d)cycloheptene-delta(sup 5,gamma)-propylamine hydrochloride; Nornaln; 549-18-8; Amitriptyline HCl; Elatrol; Etrafon; Amiprin; Saroten; Ami-Anelun; D00809; Sarotex; Tryptal; Tripta; Ro 4-1575; Trytomer; Amineurin; Vanatrip; Apo-Amitriptyline; Amilit; Triptizol; Annoyltin; Prestwick_20; Amitid; 1-propanamine, 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-, hydrochloride; Redomex; CCRIS 7092; 10,11-Dihydro-N,N-dimethyl-5H-dibenzo[a,d]cycloheptene-Delta5,gamma-propylamine hydrochloride; Limbitrol DS; Elavil hydrochloride; Elatrolet; Amitriptyline chloride; sk-Amitriptyline chloride; Laroxyl; Mitaptyline; Tryptine; Pinsanu; Anapsique; Lantron; Enafon; HSDB 3007; Adepril; Limbitrol; Belpax show less «

DrugBank

Identification

Name:	Amitriptyline
Name (isomeric):	DB00321
Drug Type:	small molecule
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.
Synonyms:	Amitriptylin; Amitryptiline; Amitriptyline Hydrochloride; Amitriptyline HCL; Amitryptyline; Amytriptiline; Amitriprolidine
Brand:	Hexathane, Saroten, Triptanol, Sylvemid, Horizon, Damilen, Adepril, Sarotex, Triptilin, Proheptadiene, Tryptizol, Elavil, Triptisol, Redomex, Laroxil, Flavyl, Amitid, Lentizol, Laroxyl, Elanil, Seroten, Damilan, Lantron, Tryptanol, Amitril, Endep, Adepress, dAmitriptyline
Brand name mixture:	Pms-Levazine 3/15 Tab(Amitriptyline Hydrochloride + Perphenazine), Proavil Tab(Amitriptyline Hydrochloride + Perphenazine), Etrafon F Tab(Amitriptyline Hydrochloride + Perphenazine), Etrafon a Tab(Amitriptyline Hydrochloride + Perphenazine), Etrafon D Tab(Amitriptyline Hydrochloride + Perphenazine), Etrafon 2 10(Amitriptyline Hydrochloride + Per... show more » Pms-Levazine 3/15 Tab(Amitriptyline Hydrochloride + Perphenazine), Proavil Tab(Amitriptyline Hydrochloride + Perphenazine), Etrafon F Tab(Amitriptyline Hydrochloride + Perphenazine), Etrafon a Tab(Amitriptyline Hydrochloride + Perphenazine), Etrafon D Tab(Amitriptyline Hydrochloride + Perphenazine), Etrafon 2 10(Amitriptyline Hydrochloride + Perphenazine), Apo Peram Tab 3-15(Amitriptyline Hydrochloride + Perphenazine), Apo Peram Tab 2-25(Amitriptyline Hydrochloride + Perphenazine), Pms-Levazine 2/25 Tab(Amitriptyline Hydrochloride + Perphenazine), Elavil Plus Tab(Amitriptyline Hydrochloride + Perphenazine), Triavil Tab(Amitriptyline Hydrochloride + Perphenazine), Pms-Levazine 4/25 Tab(Amitriptyline Hydrochloride + Perphenazine) show less «
Category:	Analgesics, Non-Narcotic, Adrenergic Uptake Inhibitors, Antidepressive Agents, Tricyclic
CAS number:	50-48-6

Pharmacology

Indication:	For the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis.
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... show more » 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). show less «
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 re... show more » 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. show less «
Absorption:	Rapidly and well absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). Peak plasma concentrations occur 2-12 hours following oral or intramuscular administration.
Protein binding:	Very highly protein bound (90% or more) in plasma and tissues
Biotransformation:	Exclusively hepatic, with first pass effect. Amitriptyline is demethylated in the liver to its primary active metabolite, nortriptyline.
Route of elimination:	Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with little unchanged drug appearing in the urine. 25-50% of a single orally administered dose is excreted in urine as inactive metabolites within 24 hours. Small amounts are excreted in feces via biliary elimination.
Half Life:	10 to 50 hours, with an average of 15 hours
Toxicity:	LD₅₀=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. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Avoid St.John's Wort.

Avoid alcohol.

Take with food to reduce irritation.

Avoid excessive quantities of coffee or tea (caffeine).

Drug interaction:

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Duloxetine	Possible increase in the levels of this agent when used with duloxetine
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias
Tranylcypromine	Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
Orciprenaline	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of orciprenaline.

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Duloxetine	Possible increase in the levels of this agent when used with duloxetine
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias
Tranylcypromine	Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
Orciprenaline	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of orciprenaline.
Isoproterenol	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of isoproterenol.
Ketoconazole	Ketoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of amitriptyline by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ketoconazole is initiated, discontinued or dose changed.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Salbutamol	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of salbutamol.
Dopamine	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dopamine.
Atazanavir	Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if atazanavir if initiated, discontinued or dose changed.
Carbamazepine	Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if carbamazepine is initiated, discontinued or dose changed.
Guanethidine	The tricyclic antidepressant, amitriptyline, decreases the effect of guanethidine.
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Cimetidine	Cimetidine may increase the effect of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if cimetidine is initiated, discontinued or dose changed.
Norepinephrine	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of norepinephrine.
Phenelzine	Possibility of severe adverse effects
Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Ephedrine	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedrine.
Moclobemide	Possible severe adverse reaction with this combination
Fluoxetine	The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluoxetine is initiated, discontinued or dose changed.
Galantamine	Possible antagonism of action
Pirbuterol	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pirbuterol.
Zolmitriptan	Use of two serotonin modulators, such as zolmitriptan and amitriptyline, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Epinephrine	The tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of epinephrine.
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Butalbital	Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as amitriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Ritonavir	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ritonavir if initiated, discontinued or dose changed.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Trospium	Trospium and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Isocarboxazid	Possibility of severe adverse effects
Fenoterol	The tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of fenoterol.
Rivastigmine	Possible antagonism of action
Trimipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Phenylephrine	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylephrine.
Voriconazole	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Butabarbital	Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like amitriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Methoxamine	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of methoxamine.
Terbinafine	Terbinafine may reduce the metabolism and clearance of Amitryptyline. Consider alternate therapy or monitor for therapeutic/adverse effects of Amytriptyline if Terbinafine is initiated, discontinued or dose changed.
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Amitriptyline, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Quinidine	Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
Sibutramine	Increased risk of CNS adverse effects
Triprolidine	Triprolidine and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Procaterol	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of procaterol.
Quinidine barbiturate	Quinidine barbiturate increases the effect of tricyclic antidepressant, amitriptyline.
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Donepezil	Possible antagonism of action
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Tramadol	Tramadol increases the risk of serotonin syndrome and seizures.
Altretamine	Risk of severe hypotension
Fluconazole	Fluconazole may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive QTc-prolonging effects may also occur. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluconazole is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
Mephentermine	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of mephentermine.
Ephedra	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedra.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Rifampin	The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if rifampin is initiated, discontinued or dose changed.
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias
Phenylpropanolamine	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylpropanolamine.
Vilazodone	Monitor for toxic effects of tricyclic antidepressants if a selective serotonin reuptake inhibitor (SSRI) is initiated or the dose is increased. The influence of the SSRI may take several days or weeks to be fully realized or resolved.
Fluvoxamine	The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluvoxamine is initiated, discontinued or dose changed.
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Dihydroquinidine barbiturate	Dihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, amitriptyline.
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Rifabutin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if rifabutin is initiated, discontinued or dose changed.
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Metaraminol	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of metaraminol.
Pseudoephedrine	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pseudoephedrine.
Trimethobenzamide	Trimethobenzamide and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Dobutamine	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dobutamine.
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Clonidine	The tricyclic antidepressant, amitriptyline, decreases the effect of clonidine.
Rasagiline	Possibility of severe adverse effects
Terbutaline	The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of terbutaline.