Unusual mechanism of hypotensive activity exerted by erytrho-1-(1-[2-(1,4-benzodioxan-2-yl)-2-OH-ET-a1-4-piperidyl)-2-benzimidazolinone (R 28935).
In the dog, erythro-1-[2-(1,4benzodioxan-2-yl)-2-OH-ET]-4-piperidyl)-2-benzimidazolinone (R 28935) lowers the blood pressure for several hours at dosages of 80 mug/kg when injected intravenously, of 10 mug/kg when injected into the vertebral artery and of 1.25 mug/kg when injected suboccipitally. No alpha- or beta-receptor blocking activity can be elicited at these doses. The carotid occlusion reflex is markedly reduced by low doses of R 28935 (40 to 80 mug/kg i.v.), whereas the pressor response elicited by electrical stimulation of the hypothalamus remains unimpaired. The hypotensive effect of R 28935 is not antagonized by piperoxan, desmethylimipramine or nalorphine. This lowering of the blood pressure is associated with a decrease of the peripheral vascular resistance and with a slight tendency towards bradycardia. It is concluded that R 28935 is a potent blood pressure lowering drug, acting on the brain stem, presumably in the pontomedullary region--although the drug has no alpha-sympathomimetic activity.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D007031:Hypothalamus / Q000502:physiology; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D004146:Dioxanes; D010880:Piperidines; C010402:R 28935; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine