Changes in liver and brain cytochrome p450 after multiple cocaine administration, alone and in combination with nifedipine.
The objective of this study was to evaluate possible changes caused by multiple cocaine administration, alone and in combination with 1,4-dihydropiridine calcium channel blocker nifedipine, on cytochrome P450 levels both in the brain and liver. The experiment was done on male Wistar rats divided in four groups: control, treated with nifedipine (5 mg kg(-1) i.p. for five days), treated with cocaine (15 mg kg(-1) i.p. for five days), and treated with nifedipine and 30 minutes later with cocaine (also for five days). Total cytochrome P450 was measured spectrometrically in liver and brain microsomes. Multiple administration of cocaine alone and in combination with nifedipine did not change the brain P450 significantly. In the liver, nifedipine significantly increased P450 by 28% vs. control. In contrast, cocaine significantly decreased P450 by 17% vs. control. In animals treated with nifedipine and cocaine, cytochrome P450 increased 11% (p<0.01) vs. control, decreased 12.5% (p<0.001) vs. nifedipine group and increased 34% (p<0.0001) vs. cocaine group. These results suggest that the cocaine and nifedipine interact at the metabolic level.
Vitcheva
Vessela
V
Laboratory of Drug metabolism and drug toxicity, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medical University, Sofia, Bulgaria. vesselavitcheva@yahoo.com
Mitcheva
Mitka
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D003577:Cytochrome P-450 Enzyme System; D003042:Cocaine; D009543:Nifedipine