Pharmacological studies on the selectivity of HV-723, a new alpha-1 adrenoceptor antagonist.
The pharmacological profile of a new alpha-1 adrenoceptor antagonist, alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)amino) propyl) benzene-acetonitrile fumarate (HV-723), was studied in vitro. In dog mesenteric arteries, HV-723, prazosin and yohimbine competitively inhibited noradrenaline-induced contraction: the pA2 value of HV-723 (9.37) was apparently larger than that of prazosin (8.22) and yohimbine (7.18). However, HV-723 showed no or only a slight inhibition on the contractile responses to 5-HT, KCl and prostaglandin F2 alpha. HV-723 also showed potent alpha-1 adrenoceptor antagonist activity in the dog mesenteric and saphenous veins. However, HV-723 showed little antagonist activity on the pre- and postsynaptic alpha-2 adrenoceptors, beta-1 and beta-2 adrenoceptors and muscarinic receptors. HV-723 also inhibited the sympathetic contraction induced by electrical transmural stimulation in the dog mesenteric arteries, and the inhibition of HV-723 was about 10 times more potent than that of prazosin. However, 3H-noradrenaline release evoked by electrical stimulation was not influenced by HV-723. These results clearly show that HV-723 is a potent and selective alpha-1 adrenoceptor antagonist.
Oshita
M
M
Research Laboratories, Hokuriku Seiyaku Co., Ltd., Fukui, Japan.
Iwanaga
Y
Y
Hashimoto
S
S
Morikawa
K
K
Muramatsu
I
I
D000097:Acetonitriles / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000097:Acetonitriles; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; C058562:HV 723; D015016:Yohimbine; D009638:Norepinephrine; D011224:Prazosin