[Pharmacological analysis of the mode of action of mandelamidine with sustained antihypertensive effect. (II). Mechanism of transient hypotensive action of mandelamidine].
The mode of a transient hypotensive action of dl-Mandelamidine (MA) was studied in both anesthetized and unanesthetized animals. In the blood pressure of unanesthetized rats, a transient hypotensive action of MA (1 approximately 30 mg/kg i.v.) like papaverine (1 approximately 10 mg/kg i.v.) was much less predominant than in rats anesthetized with urethane (1.5 g/kg s.c.). The transient hypotensive action of MA (10 mg/kg i.v.) in rats anesthetized with urethane (1.5 g/kg s.c.) was not reduced when MA was injected continuously. Moreover C6 (5 mg/kg i.v.), propranolol (1 mg/kg i.v.), diphenhydramine (10 mg/kg i.v.) and atropine (2 mg/kg i.v.) did not block this transient hypotensive action. MA blocked the pressor action of epinephrine (3 mug/kg i.v.) in three minutes, but then potentiated it. MA (10 mug/kg i.a. approximately 1 mg/kg i.a.) caused a temporary vasodilation on the perfused leg artery and vertebral artery in dogs anesthetized with sodium pentobarbital (30 mg/kg i.v.). In the perfused leg artery, atropine (2 mg/kg i.v.) and propranolol (1 mg/kg i.v.) did not block the vasodilation of MA, and MA showed no marked blocking effect of the vasoconstriction of norepinephrine (0.2 mug/kg i.a.). In the dog heart-lung preparation and the guinea-pig heart, MA showed inhibiting effects. On the contraction of the cat nictitating membrane elicited by the stimulation of the postganglionic cervical sympathetic nerve, the blocking action of MA (1 mug/kg i.a. approximately 1 mg/kg i.a.) was much less predominant than that of phentolamine (10 mug/kg i.a.). In the rabbit descending aorta, MA (3 X 10(-4) g/ml) antagonized non-competitively the contraction elicited by norepinephrine. These findings suggest that a transient hypotensive action of MA depends upon the inhibiting effects on the cardiovascular system, and the adrenergic alpha-blocking effect of MA may be very weak.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008709:Methenamine / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats
D000959:Antihypertensive Agents; D008709:Methenamine