Publication details
Pharmacokinetics of dextromethorphane in rats pretreated with methamphetamine and fluoxetine
| Authors | |
|---|---|
| Year of publication | 2002 |
| Type | Article in Periodical |
| Magazine / Source | Bratislavské lekárské listy |
| MU Faculty or unit | |
| Citation | |
| web | http://www.bmj.cz |
| Field | Pharmacology and pharmaceutical chemistry |
| Keywords | dextromethorphane; fluoxetine; methamphetamine |
| Description | The purpose of this study was to assess pharmacokinetics of dextromethorphan (model substrate of metabolism by CYP 450). Dextromethorphan was used as surrogate marker of CYP2D1 activity as it is preferentially metabolised via O-demethylation by CYP2D1 to its primary metabolite dextrorphan (DOR). CYP3A4 is responsible for N-demethylation of DEM to methoxymorphinan and of DOR to hydroxymorphinan. CYP2D1 is the homolog of human CYP2D6. Fluoxetine has been reported to be of therapeutic benefit in the treatment of alcoholism; it was the aim of the present study to compare the effect of fluoxetine (20mg/kg for 6 days i.p.)in the rats pretreated by methamphetamine (10mg/kg for 6 days i.p.), as well as to answer the question if fluoxetin may be used for the characterization of novel pharmacotherapy in methamphetamine dependence. Fluoxetine in our experiments inhibited metabolism by the CYP2D1 and the CYP3A4. Methamphetamine stimulated metabolism mediated by the CYP2D1 but not by the CYP3A4. Combination of drugs inhibited oxidative metabolism by the CYP2D1 but stimulate alternative pathway of metabolism by the CYP3A4. The results suggest that fluoxetine therapy in methamphetamine dependence could slow down biodegradation of methamphetamine and this would enable to reduce methamphetamine doses without a decrease in psychotropic effect of the drug. |
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