For the treatment of anxiety, bipolar disorders, and depression.
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.
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.
Rapidly and well absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism).
10 to 50 hours, with an average of 15 hours
Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with little unchanged drug appearing in the urine.