S. UnchernA. ThithapandhaMahidol University2018-06-012018-06-011979-01-01Drug Metabolism and Disposition. Vol.7, No.6 (1979), 411-415009095562-s2.0-0018651279https://repository.li.mahidol.ac.th/handle/20.500.14594/13287Pretreatment of rats with cyproheptadine hydrochloride (CPH, 10 mg/kg, ip, twice daily for 5 days) produced an increase in aminopyrine N-demethylase activity and a significant elevation of hepatic microsomal cytochrome P-450 content. These increases were prevented by simultaneous administration of actinomycin D (0.1 mg/kg, ip), thus suggesting that CPH was an enzyme inducer. The inductive effect reached its maximum in 3-5 days and regressed to normal in about 4 days after cessation of the drug. Kinetic and inhibition studies provided support for the concept that the enzymes from both the normal and CPH-treated livers were the same. However, this schedule of CPH pretreatment had no effect on aniline hydroxylase activity. Thus, the nature of microsomal enzyme stimulation by CPH appeared to resemble that of the phenobarbital-type inducers, except for the finding that, unlike phenobarbital, CPH did not cause any noticeable proliferation of the smooth endoplasmic reticulum. The liver cells from the CPH-treated rats revealed instead a degree of ultrastructural alteration. When examined under an electron microscope, accumulation of fatty droplets and microbody formation were readily noticeable in most cells. All of these experimental findings suggest that cyproheptadine hydrochloride may possess a weak microsomal inductive property and a certain degree of hepatotoxicity. The latter effect provides a strong argument against the previous speculation by other investigators concerning organ-specific toxicity (pancreotoxicity) of the drug in rats.Mahidol UniversityPharmacology, Toxicology and PharmaceuticsArticleSCOPUS