title: Antilipolytic effects of 1,8-naphthyridine derivatives β-adrenoceptor antagonists in rat white adipocytes.
abstract: 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.
authors.affiliation: Faculty of Pharmacy, Jerash University, Jerash, Jordan.
authors.forename: Jalal A
authors.identifier: 0000-0002-0815-8529
authors.initials: JA
authors.lastname: Aljamal
authors.affiliation: Faculty of Pharmacy, Jerash University, Jerash, Jordan.
authors.forename: Muwaffag
authors.initials: M
authors.lastname: Badawneh
mesh_terms: D052438:Adipocytes, White / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D004983:Ethanolamines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000737:chemistry / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D009287:Naphthyridines; D011943:Receptors, Adrenergic, beta; C114929:SR 59104A; D013764:Tetrahydronaphthalenes; D000526:Alprenolol; D007545:Isoproterenol
keywords: 1,8 naphthyridine; lipolysis; rat white adipocytes; β-adrenergic receptors