Amitriptyline¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ 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.
Pharmacology
Amitriptyline¿¡ ´ëÇÑ Pharmacology Á¤º¸ 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).
Amitriptyline¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Very highly protein bound (90% or more) in plasma and tissues
Half-life
Amitriptyline¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 10 to 50 hours, with an average of 15 hours
Absorption
Amitriptyline¿¡ ´ëÇÑ Absorption Á¤º¸ Rapidly and well absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism).
Biotransformation
Amitriptyline¿¡ ´ëÇÑ Biotransformation Á¤º¸ Exclusively hepatic, with first pass effect. Amitriptyline is demethylated in the liver to its primary active metabolite, nortriptyline.
Toxicity
Amitriptyline¿¡ ´ëÇÑ Toxicity Á¤º¸ 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.
Drug Interactions
Amitriptyline¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Altretamine Risk of severe hypotensionAtazanavir Atazanavir increases the effect and toxicity of tricyclicsCarbamazepine The tricyclics increases the effect of carbamazepineCimetidine Cimetidine increases the effect of tricyclic agentCisapride Increased risk of cardiotoxicity and arrhythmiasGrepafloxacin Increased risk of cardiotoxicity and arrhythmiasClonidine The tricyclic decreases the effect of clonidineDihydroquinidine barbiturate Quinidine increases the effect of tricyclic agentDobutamine The tricyclic increases the sympathomimetic effectDonepezil Possible antagonism of actionDopamine The tricyclic increases the sympathomimetic effectDuloxetine Possible increase in the levels of this agent when used with duloxetineEpinephrine The tricyclic increases the sympathomimetic effectFenoterol The tricyclic increases the sympathomimetic effectFluconazole The imidazole increases the effect and toxicity of the tricyclicFluoxetine Fluoxetine increases the effect and toxicity of tricyclicsFluvoxamine Fluvoxamine increases the effect and toxicity of tricyclicsGalantamine Possible antagonism of actionGuanethidine The tricyclic decreases the effect of guanethidineIsocarboxazid Possibility of severe adverse effectsIsoproterenol The tricyclic increases the sympathomimetic effectKetoconazole The imidazole increases the effect and toxicity of the tricyclicMetaraminol The tricyclic increases the sympathomimetic effectMesoridazine Increased risk of cardiotoxicity and arrhythmiasMethoxamine The tricyclic increases the sympathomimetic effectMoclobemide Possible severe adverse reaction with this combinationNorepinephrine The tricyclic increases the sympathomimetic effectOrciprenaline The tricyclic increases the sympathomimetic effectPhenelzine Possibility of severe adverse effectsPhenylephrine The tricyclic increases the sympathomimetic effectPhenylpropanolamine The tricyclic increases the sympathomimetic effectPirbuterol The tricyclic increases the sympathomimetic effectPseudoephedrine The tricyclic increases the sympathomimetic effectQuinidine Quinidine increases the effect of tricyclic agentQuinidine barbiturate Quinidine increases the effect of tricyclic agentRifabutin The rifamycin decreases the effect of tricyclicsRifampin The rifamycin decreases the effect of tricyclicsRitonavir Ritonavir increases the effect and toxicity of tricyclicsRivastigmine Possible antagonism of actionSibutramine Increased risk of CNS adverse effectsSparfloxacin Increased risk of cardiotoxicity and arrhythmiasTerbutaline The tricyclic increases the sympathomimetic effectTerfenadine Increased risk of cardiotoxicity and arrhythmiasThioridazine Increased risk of cardiotoxicity and arrhythmiasTranylcypromine Possibility of severe adverse effectsEphedra The tricyclic increases the sympathomimetic effectEphedrine The tricyclic increases the sympathomimetic effectMephentermine The tricyclic increases the sympathomimetic effectProcaterol The tricyclic increases the sympathomimetic effectRasagiline Possibility of severe adverse effectsSalbutamol The tricyclic increases the sympathomimetic effect
Amitriptyline¿¡ ´ëÇÑ Description Á¤º¸ 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]
The database contains the following fields: The generic name of each chemical For module A10 (liver enzyme composite module): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the number of active and marginally active scores for each compound at the five individual endpoints (see research article for full description of method) Number of endpoints at which each compound is marginally active (M) Number of endpoints at which each compound is active (A) For modules A11 to A15 (alkaline phosphatase increased, SGOT increased, SGPT increased, LDH increased, and GGT increased, respectively): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the RI and ADR values (see the research article for full description of method) Number of ADR reports for each compound, given as <4 or ¡Ã4 Reporting Index value for each compound, except where no shipping units were available (NSU) Group 1 comprises of compounds for which ADR data were available for the first five years of marketing, so when no ADR reports were listed during this period the compounds were evaluated as inactive. Group 2 comprises of compounds for which a 'steady state' period of ADR data were available (1992-1996). In cases where no ADR reports were filed during this period, the compounds were scored as 'NA' (data not available) since they may have had one or more ADR reports during their first five years of marketing which should not be negated by a lack of ADR reports during the steady-state period. AMITRIPTYLINE [GGT Increase] [Composite Activity] (Score) NA (Marginal) 0 (Active) 0
[Alkaline Phosphatase Increase] (Activity Score) NA (Number of Rpts) NA (Index value) NA
[SGOT Increase] (Activity Score) NA (Number of Rpts) NA (Index value) NA
[SGPT Increase] (Activity Score) NA (Number of Rpts) NA (Index value) NA
[LDH Increase] (Activity Score) NA (Number of Rpts) NA (Index value) NA
[GGT Increase] (Activity Score) NA (Number of Rpts) NA (Index value) NA