Mesoionic Oxatriazoles (MOTA): NO-Donating Characteristics and Pharmacology

Abstract

Biological role of nitric oxide (NO), functioning of isoforms of NO synthetases (NOS) and pharmacology of principle NO-donors were reviewed. NO donating characteristics and pharmacology of 23 mesoionic oxatriazoles (MOTA) were compared with those of 5-morpholinosydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside (NaNP) and glyceryl trinitrate (GTN). It is concluded that in vitro NO donating profile of MOTA hardly can be used as a predicting measure for their pharmacological activities either in vitro or in vivo. If anything, fast NO releasers seem to be stronger vasorelaxants than MOTA with slow NO releasing properties. Still, among representatives of this last category of MOTA one may find efficient antithrombotic and thrombolytic agents. For instance, MOTA 5-oxides were more potent thrombolytics than SIN-1, SNAP or NaNP. Also MOTA with potent anti-platelet action in vitro seem to be potent relaxants of tracheal strips. In summary, by manipulating the chemical structures of MOTA one may obtain relative selectivity towards vasorelaxant, anti-platelet, thrombolytic or tracheorelaxant properties. Thus different categories of MOTA might be designed with a hope of achieving hypotensive, antithrombotic, thrombolytic or anti-asthmatic drugs.