Effects of 2-[(5-chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434), a new alpha-adrenoceptor agonist, on pre- and postsynaptic alpha-adrenoceptors in canine mesenteric artery.
Post- and presynaptic alpha-adrenoceptors in the canine mesenteric artery show distinct features of alpha 1 and alpha 2 types, respectively. The effects of a newly synthesized pressor agent, 2-[(5-chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434), on the pre- and postsynaptic alpha-adrenoceptors of the canine mesenteric artery were examined pharmacologically. M6434 produced a contractile response in the mesenteric artery. The EC50 value of M6434 was 1.1 X 10(-7) M, that was almost the same as that of norepinephrine but significantly lower than the value seen with methoxamine. The maximum amplitude of contraction developed by M6434 was approximately 81% of that induced by norepinephrine. The contractile response to M6434 was competitively inhibited by prazosin (pA2 = 9.23 +/- 0.08) and yohimbine (pA2 = 7.85 +/- 0.09). M6434 also reduced the 3H-efflux evoked by electrical transmural stimulation in the arterial tissues preincubated with 3H-norepinephrine, and the maximum inhibition corresponded to about 60% of the case of norepinephrine. This presynaptic effect was inhibited by yohimbine but not by prazosin. The results show that M6434 is almost a full agonist for alpha 1-adrenoceptor with partial alpha 2-effect.
D000818:Animals; D004285:Dogs; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000294:innervation; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C032482:2-((5-chloro-2-methoxyphenyl)azo)-1H-imidazole; D009638:Norepinephrine; D011224:Prazosin