Development of tolerance and a new coronary vasodilator, N-(2-hydroxyethyl)nicotinamide nitrate (SG-75): A comparison with nitroglycerin.

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Abstract
Tolerance to N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) [a potential anti-anginal agent] and nitroglycerin (NTG) was studied in rats with regard to blood pressure responses in vivo and thoracic aorta strip preparations in vitro. Tolerance to the blood pressure response to SG-75 or NTG was observed with consecutive s.c. administrations of high doses of SG-75 or NTG, 3 times per day and the tolerance was time- and dose-dependent. In strips of the aorta incubated for 30 min with SG-75, sensitivity to challenging doses of SG-75 remained unchanged, but in the preparations incubated with NTG, the response to challenging doses of NTG was greatly decreased. SG-75 developed no cross-tolerance to NTG. In in vivo experiments, SG-75 induced slight tolerance, but in the in vitro experiments, unlike NTG, SG-75 induced no tolerance.