کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4315397 | 1290077 | 2008 | 6 صفحه PDF | دانلود رایگان |
Efflux transporters, like P-glycoprotein (P-gp), may limit the access of drugs to the brain via the blood–brain barrier. The antipsychotic drug risperidone and its active metabolite 9-hydroxyrisperidone (paliperidone) are substrates of P-gp. Motor behavior of P-gp deficient mice (mdr1a/1b (−/−, −/−)) and wild type animals on a rotarod after acute doses of risperidone or haloperidol, a nonsubstrate of P-gp, were analysed aiming to show that P-gp substrate properties of an antipsychotic drug have functional consequences. Behavioral tests revealed dose-dependent effects of 0.3–3 mg/kg risperidone in wild type animals 0.5–12 h after i.p. injection of the drug. In knockout mice the 0.3 mg/kg dose of risperidone was as effective as the 3 mg/kg dose in wild type mice. A dose of 0.3 mg/kg haloperidol, however, exhibited similar pharmacodynamic effects in both genotypes. Brain concentrations of risperidone plus 9-hydroxyrisperidone were 10-fold higher in knockout than in wild type animals whereas brain concentrations of haloperidol did not differ between the two genotypes. P-gp-dependent brain distribution kinetics and behavioral effects of risperidone give evidence that the expression of P-gp has an impact on psychotropic drug actions when treating patients with drugs that are substrates of P-gp.
Journal: Behavioural Brain Research - Volume 188, Issue 2, 9 April 2008, Pages 298–303