Abstract
The presence of in vitro NO-donor characteristics in the antihypertensive drugs clonidine and guanfacine, the structure of which contains a guanidine grou** that relates these drugs to arginine (the main substrate of the enzyme NO-synthase, producing NO in vivo) was established by chemical oxidation of the drugs followed by polarographic detection of the produced nitric oxide in the form of nitroprusside ion. It was shown that under the investigated conditions in vitro the NO-donor activity of clonidine and guanfacine is comparable in magnitude with the NO-donor activity of arginine. It was also found that guanfacine and clonidine (the latter in the presence of NAD+) activate the soluble guanidatecyclase enzyme, which is a characteristic indication of NO donors. It is suggested on the basis of the obtained data that clonidine and guanfacine can undergo enzymatic oxidation to NO in vivo and that the pharmacologica l action of clonidine and guanfacine may be due to some extent to the NO-donor characteristics of these drugs.
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Levina, V.I., Pyatakova, N.V., Busygina, O.G. et al. Some Antihypertensive Drugs Clonidine (Clofelin) and Guanfacine - New Nitric Oxide Donors. Chemistry of Heterocyclic Compounds 38, 1469–1474 (2002). https://doi.org/10.1023/A:1022689327005
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DOI: https://doi.org/10.1023/A:1022689327005