Amoxapine--an antidepressant with some neuroleptic properties? A review of its chemistry, animal pharmacology and toxicology, human pharmacology, and clinical efficacy.

Amoxapine, a new antidepressant, exhibits both antidepressant and neuroleptic effects in laboratory animals and in humans. Evidence from human studies (extrapyramidal reactions, hyperprolactinemia, and galactorrhea), animal screening tests, and neurochemical experiments support the contention that amoxapine or a metabolite occasionally produces neuroleptic-like effects. Amoxapine's neuroleptic activity may derive from 7-hydroxy-amoxapine, a minor metabolite in humans, which exhibits significant dopamine receptor-blocking activity. Evidence for an early antidepressant effect of amoxapine in the treatment of depressive illness has not been consistently demonstrated. In comparable doses (roughly twice the dose of imipramine or amitriptyline), amoxapine appears to be similar to reference antidepressants in efficacy, unwanted effects, and acute toxicity.