Comparison of the potentiating effects of nicorandil and its denitrated metabolite (SG-86) on the adenosine-induced vasodepression in rats.
The potentiating activity of SG-86[N-(2-hydroxyethyl)nicotinamide], a denitrated metabolite of nicorandil, on the adenosine-induced vasodepression was compared with that of nicorandil in anesthetized rats. Single bolus i.v. adenosine (3-100 micrograms/kg) produced dose-dependent reductions of blood pressure, accompanied by slight decreases (except for 100 micrograms/kg) in heart rate. The adenosine-induced vasodepression was significantly enhanced during i.v. infusion of either SG-86 (100 micrograms/kg per min) as well as nicorandil (10 micrograms/kg per min). The enhancement of adenosine action by them did not occur in the presence of glibenclamide (20 mg/kg i.v.). Single bolus i.v. injections of SG-86 (0.3-30 mg/kg), except for 30 mg/kg, which caused a glibenclamide-sensitive decrease by about 5-10 mmHg in mean arterial blood pressure, had no effects on blood pressure and heart rate, whereas those of nicorandil (30-300 micrograms/kg) elicited overt reduction of blood pressure, accompanied by decreases in heart rate. The present results revealed that SG-86, like nicorandil, significantly enhanced the vasodepressor response to adenosine, probably in part through KATP channel activation, and that the activity of SG-86 was about 10 times less potent than that of nicorandil.
Sakai
K
K
Central Research Laboratories, Chugai Pharmaceutical Co, Ltd, Tokyo, Japan.
Saito
K
K
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; C030731:N-(2-hydroxyethyl)nicotinamide; D000241:Adenosine; D005905:Glyburide