In vitro pharmacological profile of the novel alpha 1-adrenoceptor antagonist HSR-175.
The pharmacological profile of HSR-175, a new alpha 1-adrenoceptor antagonist, was studied in vitro and compared with those of other alpha 1-antagonists. HSR-175, prazosin, bunazosin and yohimbine competitively antagonized the contractile responses induced by noradrenaline in the dog mesenteric arteries and the rabbit thoracic aorta. The pA2 values for HSR-175 in the dog mesenteric arteries and the rabbit aorta were 10.38 and 9.63, respectively, which were significantly higher than those for prazosin (8.39 and 8.80), bunazosin (8.44 and 8.75) and yohimbine (7.34 and 6.10). HSR-175 also inhibited the sympathetic adrenergic contraction induced by electrical transmural stimulation in the dog mesenteric arteries, and the inhibitory effect of HSR-175 was more potent than those of prazosin and bunazosin. Although HSR-175 also possessed competitive antagonist properties at pre- and postsynaptic alpha 2-adrenoceptors in the rat vas deferens and the dog saphenous veins, those affinities (pA2 = 6.41 and 7.05) were much lower than those at postsynaptic alpha 1-adrenoceptors. Furthermore, HSR-175 at concentration of 10(-6) M showed no inhibition on the contractile responses to 5-HT, histamine, KCl and angiotensin II in the rabbit thoracic aorta. These results indicate that HSR-175 is a very potent and selective alpha 1-adrenoceptor antagonist.
Central Research Laboratories, Hokuriku Seiyaku Co., Ltd., Fukui, Japan.
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S
Hashimoto
M
M
Oshita
K
K
Morikawa
H
H
Kato
Y
Y
Ito
S
S
Kigoshi
I
I
Muramatsu
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D000096926:Benzenesulfonamides
D000317:Adrenergic alpha-Antagonists; D005464:Fluorobenzenes; D013449:Sulfonamides; C077872:HSR 175; D000096926:Benzenesulfonamides