title: Anti-hypotensive effects of M6434, an orally active alpha 1-adrenoceptor agonist, in rats.
abstract: The anti-hypotensive effects of M6434 were evaluated and compared with those of other orally active sympathomimetics in rats. Oral administration of M6434 (0.5-2.0 mg/kg) and midodrine (1.0-5.0 mg/kg) also produced a dose-related increase in mean arterial pressure in normotensive rats. The pressor effect of M6434 was about 4 times more potent than that of midodrine. Both M6434 and midodrine caused a dose-dependent decrease in heart rate. The pressor effect of M6434 (1.0 mg/kg) did not diminish after its repeated administration for 7 days. The pretreatment with M6434 (0.5-1.0 mg/kg) and midodrine (2.0-5.0 mg/kg) improved the orthostatic index in the experimental model of postural hypotension in rats. The effect of M6434 on postural hypotension was about 5 times more potent than that of midodrine. Intravenously injected M6434 (3-300 micrograms/kg) produced a dose-dependent increase in the blood pressure of pithed rats. These results suggest that M6434 possesses a potent antihypotensive activity which is superior to that of midodrine, and M6434 may be useful in the treatment of essential and postural hypotension.
mesh_terms: D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D004087:Dihydroergotamine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000188:drug therapy*; D007024:Hypotension, Orthostatic / Q000188:drug therapy; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008879:Midodrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D004087:Dihydroergotamine; D008879:Midodrine; C032482:2-((5-chloro-2-methoxyphenyl)azo)-1H-imidazole