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Comparison of the potentiating effects of nicorandil and its denitrated metabolite (SG‐86) on the adenosine‐induced vasodepression in rats
Author(s) -
Sakai K,
Saito K
Publication year - 1998
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1998.tb00977.x
Subject(s) - nicorandil , glibenclamide , adenosine , metabolite , chemistry , blood pressure , heart rate , bolus (digestion) , endocrinology , medicine , nicotinamide , pharmacology , biochemistry , enzyme , diabetes mellitus
Summary— 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 iv adenosine (3–100 μg/kg) produced dose‐dependent reductions of blood pressure, accompanied by slight decreases (except for 100 μg/kg) in heart rate. The adenosine‐induced vasodepression was significantly enhanced during iv infusion of either SG‐86 (100 μg/kg per min) as well as nicorandil (10 μg/kg per min). The enhancement of adenosine action by them did not occur in the presence of glibenclamide (20 mg/kg iv). Single bolus iv injections of SG‐86 (0.3–30 mg/kg), except for 30 mg/kg, which caused a glibenclamide‐sensitive decrease by about 5–10 mm Hg in mean arterial blood pressure, had no effects on blood pressure and heart rate, whereas those of nicorandil (30–300 μg/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 K ATP channel activation, and that the activity of SG‐86 was about 10 times less potent than that of nicorandil.