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

Tolerance to N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) and nitroglycerin (NTG) was studied in rats with regard to the 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 subcutaneous administrations of high doses of SG-75 or NTG, three times a 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 developed only slight tolerance, but in the in vitro experiments, unlike NTG, induced no tolerance.