Antihypertensive effects of a novel phenylpiperazine derivative, SGB-1534, on several hypertensive models of rats.
The antihypertensive activities of SGB-1534, 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4 (1H,3H)-quinazolinedione monohydrochloride, compared with prazosin, were examined in anesthetized or conscious hypertensive rat models. In anesthetized rats, SGB-1534 administered orally (3-10 mg/kg) reduced the blood pressure and significantly inhibited the pressor response to noradrenaline, but did not affect blood pressure responses to angiotensin II, isoproterenol, histamine and acetylcholine. This compound (0.1-3 mg/kg, p.o.) exhibited potent and long-lasting antihypertensive effects in conscious spontaneously hypertensive rats (SHRs), renal hypertensive rats and DOCA-salt rats, but it increased the heart rate only minimally. Repeated p.o. doses of SGB-1534 also reduced the blood pressure in SHRs without noticeable sign of tolerance to antihypertensive effects. In an experimental model for determining blood pressure compensation for postural tilt in anesthetized rats, SGB-1534 was free of postural effects, while prazosin induced orthostatic hypotension. In renal hypertensive rats and SHRs, SGB-1534, unlike prazosin, caused no increase in plasma renin activity. The present results reveal some pharmacological characteristics of SGB-1534 as an orally effective antihypertensive agent.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000633:toxicity; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D006977:Hypertension, Renal / Q000188:drug therapy; D007928:Lethal Dose 50; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011187:Posture; D011224:Prazosin / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood
D000959:Antihypertensive Agents; D011799:Quinazolines; D003900:Desoxycorticosterone; C042712:SGB 1534; D012083:Renin; D011224:Prazosin; D010646:Phentolamine