Pharmacological studies on 3-[gamma-(p-fluorobenzoyl)propyl]-2,3,4,4a,5,6-hexahydro-1-(H)-pyrazino (1,2-a) quinoline (compound 69/183). Part I: Hypotensive activity.
3-[gamma-(p-Fluorobenzoyl)propyl]-2,3,4,4a,5,6-hexahydro-1-(H)-pyrazinol(1,2-a)quinoline (compound 69/183, centpyraquin) has been found to possess promising hypotensive activity in anaesthetised cat, dog and monkey- It also lowers the blood pressure of unanaesthetised cat, dog and hypertensive rat. The effective doses are between 0.5 to 2.0 mg/kg in all the species except rat, in which doses of 10.0 and 20.0 mg/kg are effective. The compound potentiates epinephrine and norepinephrine pressor responses but inhibits carotid occlusion, tyramine and DMPP induced pressor responses. The contraction of the nictitating membrane due to pre- as well as post-ganglionic sympathetic nerve stimulation is blocked equally. In mice the compound produces ptosis which is antagonised by N-benzyl-N-methylguanidine. Localisation of the compound either to the superior cervical ganglion of cat or to the central cardiovascular loci has no effect on the activities of either of them. No evidence of an initial catecholamine release by the compound could be obtained. It has weak smooth muscle relaxant activity. The mechanism of hypotensive action seems to be the blockade of adrenergic neurones along with direct smooth muscle relaxation.
D000311:Adrenal Glands; D000818:Animals; D000959:Antihypertensive Agents; D001763:Blepharoptosis / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects*; D002090:Butyrophenones / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002415:Cats; D004068:Digestive System Physiological Phenomena; D005260:Female; D005728:Ganglia, Sympathetic; D006146:Guanidines / Q000031:analogs & derivatives*; D000882:Haplorhini; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007267:Injections; D007269:Injections, Intra-Arterial; D007276:Injections, Intraventricular; D008297:Male; D008760:Methylguanidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011804:Quinolines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D013116:Spinal Cord / Q000502:physiology
D000959:Antihypertensive Agents; D002090:Butyrophenones; D006146:Guanidines; D006584:Hexamethonium Compounds; D011804:Quinolines; D008760:Methylguanidine