Antilipolytic activity of tiadenol-nicotinate in isolated fat cells: a comparison with its parent drugs.
Tiadenol-nicotinate is an ester in which two molecules of nicotinic acid are linked to one molecule of tiadenol. In the present study the antilipolytic activity of tiadenol-nicotinate was evaluated in isolated rat fat cells and a direct comparison was made with the parent drugs. Basal lipolysis was not affected by tiadenol-nicotinate or by nicotinic acid, but it was reduced by a high concentration of tiadenol (10(-3) M) alone or associated with a double concentration of nicotinic acid. Tiadenol-nicotinate (10(-5)-10(-3) M) was very effective in antagonizing the lipolytic action of epinephrine (10(-6) M) and of theophylline (3 X 10(-4) M). The latter drugs were equally sensitive to the inhibitory effect of tiadenol, while nicotinic acid reduced the action of theophylline more than the effect of the catecholamine. Neither of the parent drugs was as effective as tiadenol-nicotinate at this level. However, nicotinic acid potentiated the antilipolytic effect of tiadenol, thus making it possible to reach an inhibitory effect quantitatively similar to or even higher than the effect of tiadenol-nicotinate. These results show that tiadenol-nicotinate is a potent antilipolytic agent in vitro and that its effect may be due to hydrolysis of the ester and release of the parent drugs. The possible therapeutic value of tiadenol-nicotinate is discussed.
D000273:Adipose Tissue / Q000187:drug effects*; D000818:Animals; D004338:Drug Combinations; D004837:Epinephrine / Q000494:pharmacology; D005233:Fatty Alcohols / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D009525:Niacin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000494:pharmacology
D004338:Drug Combinations; D005233:Fatty Alcohols; C004568:tiadenol; D009525:Niacin; D013806:Theophylline; D004837:Epinephrine