Pharmacological Profile of a New Coronary Vasodilator Drug, 2-Nicotinamidoethyl Nitrate (Sg-75)

Abstract

1. In anaesthetized, open-chest dogs, 2-nicotinamidoethyl nitrate (SG-75) administered intravenously (0.3-1 mg/kg) or intraduodenally (3 mg/kg) produced decrease in systemic blood pressure, coronary resistance, heart rate and an increase in coronary sinus outflow, but virtually no change in myocardial oxygen consumption and atrioventricular conduction. The effects of SG-75 administered intraduodenally emerged within a few minutes after dosing and lasted over about 1 h. 2. In isolated, blood-perfused sino-atrial node preparations of the dog SG-75 administered into the sinus node artery decreased slightly sinus rate at the dose which doubled blood flow through the artery. 3. In isolated, blood-perfused atrioventricular node preparations of the dog SG-75 administered into the atrioventricular node artery did not impair atrioventricular conduction even in doses which increased blood flow through the artery to more than twice the basal level. 4. In isolated, blood-perfused papillary muscle preparations of the dog SG-75 administered into the anterior septal artery scarely affected force of contraction of the papillary muscle at the dose which doubled blood flow through the artery, although in further large doses it produced a transient decrease in the force of contraction. In extremely large doses it produced ventricular fibrillation. 5. In anaesthetized, open-chest dogs in which cardiac input was kept constant SG-75 (0.01-1 mg/kg) administered into the ascending aorta increased venous return without changing systemic output. 6. 2-Nicotinamidoethyl alcohol, a denitrated compound of SG-75, had no vasodilator action in doses comparable to those of the parent compound. 7. These results indicate SG-75 to be a potential antianginal drug having no cardiodepressant actions but having properties uncharacteristic of the nitrates.

Nicorandil attenuates myocardial acidosis during coronary occlusion in dogs

“…This beneficial action of nicorandil on the ischaemic myocardium is shared by nitroglycerine and propranolol but not by dipyridamole (Ichihara et al, 1979;Abiko & Sakai, 1980;Shibano & Abiko, 1983). The beneficial action of nicorandil is probably because of the coronary vasodilator effect of the drug (Uchida et al, 1978;Taira, et al, 1979;Sakai et al 1981), permitting an increase in perfusion of the ischaemic area by increased blood supply from the non-ischaemic area, in which blood flow has been increased. This assumption is based on the findings of Ogawa et al, 1982.…”

Comparative effects of nicorandil and nitroglycerin on tracheal and vascular smooth muscle in the dog, in vivo and in vitro.

“…This is consistent with the finding of Maruyama et al (7) that nicorandil has a potent broncho-dilating activity. It has been reported that nicorandil has a nitrate moiety in its chemical structure which plays an important role in the pharmacological activity of this drug (2,5). Recently, Maru yama et al (7) also confirmed that in the arterially blood-perfused preparation of the dog trachea in situ, the nitrate site of nicorandil plays an important role in in creasing its activity to produce both tracheal dilatation and tracheal vasodilation.…”

“…Thus, it seems that NCR has a relatively selective action on the vasculature. This compound has a nitrate moiety in its chemical structure, and this site undoubtedly plays an important role in the development of its pharmacological activity (2,5). Recently, the effects of locally applied nitroglycerin (NTG) (6) and NCR (7) on the tracheal musculature and vasculature were investi gated in the arterially blood-perfused pre paration of the dog trachea (8).…”

Specific but differential antagonism by glibenclamide of the vasodepressor effects of cromakalim and nicorandil in spinally‐anaesthetized dogs

“…Recently, it has also been shown that in rats the vasodepressor effect of cromakalim on systemic arterial pressure was specifically antagonized by glibenclamide, an oral antidiabetic drug (Cavero et al, 1988). Nicorandil exerts a vasodepressor effect (Uchida et al, 1978;Taira et al, 1979;Sakai et al, 1981) (Fleckenstein, 1981) and nearly equipotent to nicorandil as a vasodilator (Sakai et al, 1981).…”