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In order to study whether a part of the antihypertensive action of orally administered diltiazem is mediated by the central nervous system and whether metabolites of diltiazem contribute to the actions of diltiazem, we compared the effects of diltiazem and its main metabolites on blood pressure by intravenous administration with those by intracerebroventricular administration to spontaneously hypertensive rats (SHR). Contents of diltiazem and its metabolites in the brain of SHR after oral administration were also studied. Hypotensive action of intravenously administered diltiazem was stronger than that of its main metabolites in terms of potency and durability. Diltiazem (30 micrograms or more) and its main metabolites (100 micrograms) showed weak hypotensive action by intracerebroventricular administration. Oral administration of diltiazem (30 mg/kg) decreased mean blood pressure by about 40 mmHg 30 min after the administration. At this time, contents of unchanged form and metabolites of diltiazem in the brain were 0.78 +/- 0.10 and 7.58 +/- 0.89 micrograms/whole brain, respectively. It was suggested that hypotensive action of diltiazem was mainly attributable to the unchanged form and that the contribution of central action to the acute hypotensive action of diltiazem was unlikely, although centrally administered diltiazem can cause systemic hypotension.

journal of pharmacobio-dynamics

Hypotensive response of spontaneously hypertensive rats to centrally administered diltiazem and its metabolites: In relevance to the hypotensive action by oral administration.