Detail of "3250-74-6"

Reference

The development of tolerance to antilipolytic agents in rats

The development of tolerance to antilipolytic agents in rats. Myles, David D.; Stratton, Garry D.; Strong, Peter; Skidmore, Ian F. (Dep. Biochem., Glaxo Group Res., Ware/Hertfordshire SG12 0DJ, UK). Biochem. Pharmacol., 34(2), 269-74 (English) 1985. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The development of tolerance to the action of certain antilipolytic agents has been investigated in vivo in rats. Tolerance to oral nicotinic acid [59-67-6] developed during twice daily dosing for 4 days at 100 and 250 mg/kg but not at 10, 25 or 50 mg/kg. Tolerance induced by high doses of nicotinic acid was no longer detectable after a further week without treatment. Tolerance developed to a dose of 10 mg/kg nicotinic acid when dosing was repeated at hourly intervals for up to 6 h. Rats made tolerant to nicotinic acid also became tolerant to both 5-methylpyrazole-3-carboxylic acid [402-61-9] and to pyridyl-3-tetrazole [3250-74-6] and rats made tolerant to these antilipolytic agents were also tolerant to nicotinic acid. Rats made tolerant to nicotinic acid still responded to the antilipolytic activity of the prostaglandin analog, sulprostone [60325-46-4]. Apparently, nicotinic acid, pyridyl-3-tetrazole, and 5-methylpyrazole-3-carboxylic acid act through a common mechanism or receptor and the development of tolerance is assocd. with this receptor or the mechanism by which it is linked to adenylate cyclase.

The development of tolerance to antilipolytic agents by isolated rat adipocytes

The development of tolerance to antilipolytic agents by isolated rat adipocytes. Stratton, Garry D.; Myles, David D.; Strong, Peter; Skidmore, Ian F. (Dep. Biochem., Glaxo Group Res., Ware/Hertfordshire SG12 0DJ, UK). Biochem. Pharmacol., 34(2), 275-9 (English) 1985. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Using an isolated rat epididymal adipocyte system the development of tolerance to and cross-tolerance between nicotinic acid [59-67-6], 5-methylpyrazole-3-carboxylic acid [402-61-9] and pyridyl-3-tetrazole [3250-74-6] was studied. Preincubating isolated adipocytes with any 1 of these compds. resulted in a redn. of the antilipolytic activity of that compd. when the cells were exposed to a subsequent challenge dose. Furthermore, preincubation with nicotinic acid, 5-methylpyrazole-3-carboxylic acid or pyridyl-3-tetrazole resulted in a redn. of the antilipolytic response to challenge with either of the other 2 compds. Preincubation of isolated adipocytes with nicotinic acid did not affect the subsequent antilipolytic activity of the PGE2 analogs, sulprostone [60325-46-4]. Preincubation with sulprostone did not lead to the development of tolerance to its own antilipolytic actions. Apparently, nicotinic acid, 5-methylpyrazole-3-carboxylic acid and pyridiyl-3-tetrazole exert their antilipolytic activity via a common biochem. pathway which is distinct from that mediating the antilipolytic activity of prostaglandins. Apparently, the development of tolerance appears to occur prior to the involvement of adenylate cyclase in lipolysis.