Antilipolytic effects of 1,8-naphthyridine derivatives β-adrenoceptor antagonists in rat white adipocytes.
The rat fat cell β-adrenoceptors were investigated by studying the effects of new 1,8-naphthyridine derivatives synthesized starting from 7-amino-2-chloro-3-phenyl-1,8-naphthyridine on lipolysis induced by isoprenaline, and alprenolol. Lipolysis induced by isoprenaline agonist was competitively antagonized by the 1,8-naphthyridine analogue with a 7-hydroxy-2-(4'-methoxybenzylamine)-6-nitro-3-phenyl substituent designated as 3. In contrast, 10, 50, and 100 μm of 7-methoxy and 7-ethoxy derivatives did not modify the concentration-response curve of isoprenaline. A rightward shift of the curve was, however, observed with 50 μm of a 7-methoxy-2-(4'-methoxybenzylamine)-6-amino-3-phenyl substituent designated as 10. The selective β1 -AR antagonist, 7-hydroxy-4-morpholinomethyl-2-piperazino-1,8-naphthyridine slightly reduced isoprenaline-induced lipolysis only at high doses. Alprenolol-mediated lipolytic effect was antagonized by derivative 3, 10 and the selective β3 -AR antagonist SR 59,230A, but resistant to the selective β1 -AR antagonist 7-hydroxy-4-morpholinomethyl-2-piperazino-1,8-naphthyridine. The results provide preliminary pharmacological evidence for the antilipolytic effect of the newly synthesized 1,8-naphthyridine derivatives on rat fat cells. The analogues designated as 3 and 10 were the most potent antagonists of this series.
['Aljamal|Jalal A|JA|0000-0002-0815-8529', 'Badawneh|Muwaffag|M|']
D052438:Adipocytes, White D000318:Adrenergic beta-Agonists D000319:Adrenergic beta-Antagonists D000526:Alprenolol D000818:Animals D004983:Ethanolamines D007545:Isoproterenol D008066:Lipolysis D009287:Naphthyridines D051381:Rats D011943:Receptors, Adrenergic, beta D013764:Tetrahydronaphthalenes
rat white adipocytes lipolysis 1,8 naphthyridine β-adrenergic receptors