ddjd
Member
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- Jul 13, 2014
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i wonder if this explains why cyproheptadine causes me such bloating and weight gain:
Inhibition of Insulin Synthesis by Cyproheptadine: Effects on Translation 1 Present address: U.S. Environmental Protection Agency, Ariel Rios Building—2842T, 1200 Pennsylvania Ave., N.W., Washington, DC 20460.
The diabetogenic compound cyproheptadine (CPH) is known to inhibit insulin synthesis and deplete rat pancreatic insulin content in intact animals, isolated pancreatic islets, and in clonal insulin-producing cells (Chow et al., 1990; Halban et al., 1979; Hintze et al., 1977b; Miller and Fischer, 1990; Rickert et al., 1975).
Evidence that drug metabolites are involved in cyproheptadine-induced loss of pancreatic insulin. - PubMed - NCBI
Abstract
The effects of pretreatment with inhibitors of drug metabolism on the biotransformation of cyproheptadine (CPH) and the ability of the drug to deplete pancreatic insulin were investigated. CPH (45 mg/kg p.o.) or water was given once daily for 2 days to rats. SKF-525A (beta-diethylaminoethyl-2,2-diphenylpentanoate) (40 mg/kg i.p.) or water was administered 0.5 hr before the CPH treatment, and the animals were sacrificed 6 hr after the second dose of CPH. The pancreatic insulin concentration was determined, and the levels of CPH and its metabolites in pancreas, liver and lung were measured. It was found that SKF-525A pretreatment significantly protected rats from the insulin loss induced by CPH; SKF-525A alone had no effect on pancreatic insulin. The tissues from animals pretreated with SKF-525A, when compared with those of the control, had 10-fold higher levels of CPH, significantly lower concentrations of the metabolite desmethylcyproheptadine-10,11-epoxide (DMCPH-epoxide) and no change in the levels of desmethylcyproheptadine (DMCPH). The in vivo N-demethylation of N-[methyl-14C]CPH, as measured by the excretion rate of 14CO2, also was inhibited by SKF-525A pretreatment. Similar experiments were performed with another inhibitor of drug metabolism, 3,5-diethoxycarbonyl-2,6-dimethyl-4-ethyl-1,4-dihydropyridine (DDEP, 50 mg/kg i.p.); and the same results were obtained. In other experiments using DMCPH as the insulin-depleting compound, SKF-525A or DDEP pretreatment also afforded significant protection against chemical-induced insulin loss.(ABSTRACT TRUNCATED AT 250 WORDS).
Inhibition of Insulin Synthesis by Cyproheptadine: Effects on Translation 1 Present address: U.S. Environmental Protection Agency, Ariel Rios Building—2842T, 1200 Pennsylvania Ave., N.W., Washington, DC 20460.
The diabetogenic compound cyproheptadine (CPH) is known to inhibit insulin synthesis and deplete rat pancreatic insulin content in intact animals, isolated pancreatic islets, and in clonal insulin-producing cells (Chow et al., 1990; Halban et al., 1979; Hintze et al., 1977b; Miller and Fischer, 1990; Rickert et al., 1975).
Evidence that drug metabolites are involved in cyproheptadine-induced loss of pancreatic insulin. - PubMed - NCBI
Abstract
The effects of pretreatment with inhibitors of drug metabolism on the biotransformation of cyproheptadine (CPH) and the ability of the drug to deplete pancreatic insulin were investigated. CPH (45 mg/kg p.o.) or water was given once daily for 2 days to rats. SKF-525A (beta-diethylaminoethyl-2,2-diphenylpentanoate) (40 mg/kg i.p.) or water was administered 0.5 hr before the CPH treatment, and the animals were sacrificed 6 hr after the second dose of CPH. The pancreatic insulin concentration was determined, and the levels of CPH and its metabolites in pancreas, liver and lung were measured. It was found that SKF-525A pretreatment significantly protected rats from the insulin loss induced by CPH; SKF-525A alone had no effect on pancreatic insulin. The tissues from animals pretreated with SKF-525A, when compared with those of the control, had 10-fold higher levels of CPH, significantly lower concentrations of the metabolite desmethylcyproheptadine-10,11-epoxide (DMCPH-epoxide) and no change in the levels of desmethylcyproheptadine (DMCPH). The in vivo N-demethylation of N-[methyl-14C]CPH, as measured by the excretion rate of 14CO2, also was inhibited by SKF-525A pretreatment. Similar experiments were performed with another inhibitor of drug metabolism, 3,5-diethoxycarbonyl-2,6-dimethyl-4-ethyl-1,4-dihydropyridine (DDEP, 50 mg/kg i.p.); and the same results were obtained. In other experiments using DMCPH as the insulin-depleting compound, SKF-525A or DDEP pretreatment also afforded significant protection against chemical-induced insulin loss.(ABSTRACT TRUNCATED AT 250 WORDS).
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