Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class. The mechanism of clinical action of amoxapine in man is not well understood. Amoxapine is not a monoamine oxidase (MAO) inhibitor. In animals, amoxapine inhibits the re-uptake of norepinephrine and, to a lesser degree, of serotonin, at adrenergic nerve endings and blocks the response of dopamine receptors to dopamine. Its major metabolite, 8-hydroxyamoxapine, has similar norepinephrine uptake inhibiting activity but greater serotonin blocking effect than the parent compound, while the other major metabolite, 7-hydroxyamoxapine, has a dopamine receptor blocking effect.

Amoxapine is absorbed rapidly and reaches peak blood levels approximately 90 minutes after ingestion. It has a serum elimination half-life of 8 hours and is almost completely metabolized in the liver to 7-hydroxyamoxapine and 8-hydroxyamoxapine. The major active metabolite, 8-hydroxyamoxapine, has a serum half-life of 30 hours, while 7-hydroxyamoxapine is present in serum only in low concentrations with a half-life of 6.5 hours. Most of the drug is excreted in the urine and smaller amounts in the feces. The urinary metabolites appear in conjugated form as glucuronides with 33% of the dose accounted for as the 8-hydroxy metabolite and 25% as the 7-hydroxy metabolite. Only 2% is excreted unchanged. In vitro tests show that amoxapine binding to human serum protein is approximately 90%. The drug crosses the placental barrier and is excreted in human milk. The initial clinical effect usually occurs within 2 weeks of administration, but may be seen in some patients within 4 to 7 days.