title: Nifedipine lowers cocaine-induced brain and liver enzyme activity and cocaine urinary excretion in rats.
abstract: The aim of this study was to see how nifedipine counters the effects of cocaine on hepatic and brain enzymatic activity in rats and whether it affects urinary excretion of cocaine. Male Wistar rats were divided in four groups of six: control, nifedipine group (5 mg kg-1i.p. a day for five days); cocaine group (15 mg kg-1i.p. a day for five days), and the nifedipine+cocaine group. Twenty-four hours after the last administration, we measured neuronal nitric oxide synthase (nNOS) activity in the brain and cytochrome P450 quantity, ethylmorphine-N-demethylase, and anilinehydroxylase activity in the liver. Urine samples were collected 24 h after the last cocaine and cocaine+nifedipine administration. Urinary cocaine concentration was determined using the GC/MS method.Cocaine administration increased brain nNOS activity by 55 % (p<0.05) in respect to control, which indicates the development of tolerance and dependence. In the combination group, nifedipine decreased the nNOS activity in respect to the cocaine-only group.In the liver, cocaine significantly decreased and nifedipine significantly increased cytochrome P450, ethylmorphine-N-demethylase, and anilinehydroxylase in respect to control. In combination, nifedipine successfully countered cocaine effects on these enzymes.Urine cocaine excretion in the cocaine+nifedipine group significantly dropped (by 35 %) compared to the cocaine-only group.Our results have confirmed the effects of nifedipine against cocaine tolerance and development of dependence, most likely due to metabolic interactions between them.
authors.affiliation: Department of Pharmacology, Pharmacotherapy and Toxicology, Medical University Sofia, Bulgaria. vesselavitcheva@yahoo.com
authors.forename: Vessela
authors.initials: V
authors.lastname: Vitcheva
authors.forename: Rumyana
authors.initials: R
authors.lastname: Simeonova
authors.forename: Dima
authors.initials: D
authors.lastname: Karova
authors.forename: Mitka
authors.initials: M
authors.lastname: Mitcheva
mesh_terms: D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology*; D003042:Cocaine / Q000633:toxicity* / Q000652:urine; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003577:Cytochrome P-450 Enzyme System; D052248:Nitric Oxide Synthase Type I; D000815:Aniline Hydroxylase; D005037:Ethylmorphine-N-Demethylase; D005978:Glutathione; D003042:Cocaine; D009543:Nifedipine