Effect of interaction between the tricyclic antidepressant [Doxepin] and the B-adrenoceptor blocker [timolol] on the brain monoamines and systemic arterial blood pressure. [Experimental and clinical study]

ABSTRACT

Daily oral administration of timolol 5 mg/kgm for 2 weeks in albino rats produced significant increase in whole brain [A] and [NA] concentration while [5-HT] was significantly reduced. Doxepin administration 10 mg/kgm/day orally for 2 weeks induced significant increase of rat whole brain [A] and significant reduction of [NA] and [5-HT]. The effects of concurrent timolol and doxepin administration on brain [A], [NA] and [5-HT] were similar to effects of timolol but of less magnitude. In patients with mild to moderate hypertension timolol oral therapy [10 mg b.i.d.] induced a highly significant reduction of both diastolic and systolic pressures, while doxepin therapy 25 mg b.i.d. orally for 2 weeks alone or concurrently with timolol [10 mg b.i.d.] induced just significant reduction of diastolic pressure but the systolic pressure was insignificantly lowered, these effects were significantly less than the effects of timolol therapy alone. The effects of timolol or doxepin therapy as well as the effects of interaction between them on the arterial blood pressure could be partly explained by the changes induced by these druge in the brain monoamines estimated in the present work