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.