The effects of
SGB-483, a newly-synthesized hypotensive agent, on the blood pressure were studied in unanesthetized and anesthetized rats.
SGB-483 produced a significant hypotensive action in the conscious SHR and renal hypertensive (clipping) rats, and it caused reversal of the pressor response to
adrenaline in the anesthetized Wistar-Imamichi rats, SHR, and clipping rats. In an isolated guinea pig aorta preparation,
SGB-483 competitively inhibited the contractile response to
phenylephrine with a pA2 value of 7.64 +/- 0.08. In pithed rats that were pretreated with beta-
adrenoceptor blocker, the pressor effect of
adrenaline (1 microgram/kg) was not completely blocked by either
prazosin (1 mg/kg), an alpha 1-selective blocker, or
yohimbine (1 mg/kg), an alpha 2-selective blocker.
SGB-483 (1 mg/kg) had no effects on the
prazosin-resistant part of the pressor effect of
adrenaline, but significantly inhibited the
yohimbine-resistant part.
Clonidine-induced reversal of the
tachycardia induced in the pithed rat by cardiac sympathetic nerve stimulation was unaffected by
SGB-483, indicating that
SGB-483 is a selective antagonist of the alpha 1-adrenoceptor.