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Effects of a newly synthesized alpha-adrenoceptor blocking agent, 3-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-1H, 3H)-quinazoline-2, 4-dione monochloride (SGB1534), on the electrical and mechanical properties of smooth muscles of guinea-pig mesenteric artery and on the electrical properties of smooth muscles of rat tail artery were investigated. SGB1534 (10(-10) M-10(-5) M) did not modify the membrane potential and ionic conductance of the membrane in guinea-pig mesenteric artery, but this agent did inhibit depolarizations induced by noradrenaline, phenylephrine, or histamine with similar potencies. This agent inhibited serotonin-induced depolarization, but with a weak potency. In rat tail artery, the noradrenaline-induced depolarization (10(-5) M) was inhibited by yohimbine (5 X 10(-7) M), but not by SGB1534 (10(-6) M). SGB1534 (10(-6) M) did not modify the amplitude of excitatory junction potentials (e.j.ps), the facilitation process or spike potential evoked by perivascular nerve stimulation in the mesenteric artery. Noradrenaline, phenylephrine or histamine evoked the contraction in guinea-pig mesenteric artery, and this contraction was inhibited by SGB1534 (over 10(-10) M). The serotonin-induced contraction was inhibited by higher concentrations of SGB1534 (over 10(-6) M). The concentration of SGB1534 required to inhibit the contractions evoked by these amines was much higher than that required to inhibit the depolarizations. SGB1534 (less than 10(-6) M) had no effect on the excess K-induced depolarization and contraction. These results indicate that SGB1534 possesses the property of an alpha 1-but not alpha 2-adrenoceptor blocking agent.(ABSTRACT TRUNCATED AT 250 WORDS)

japanese journal of pharmacology/japanese journal of pharmacology

Effects of a New Alphai-Adrenoceptor Blocking Agent, 3-[2-[4-(2-Methoxyphenyl)-1-Piperazinyl]Ethyl]-(1H,3H)-Quinazoline-2,4-Dione Monohydrochloride (SGB1534), on Electrical and Mechanical Properties of Guinea-pig Mesenteric Artery