In vitro P-glycoprotein affinity for atypical and conventional antipsychotics.
Article Details
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Boulton DW, DeVane CL, Liston HL, Markowitz JS
In vitro P-glycoprotein affinity for atypical and conventional antipsychotics.
Life Sci. 2002 May 31;71(2):163-9.
- PubMed ID
- 12031686 [ View in PubMed]
- Abstract
The transmembrane transporter P-glycoprotein (P-gp) is an ATP-dependent efflux pump for a wide range of drugs. P-gp potentially limits access to brain tissue of psychoactive substrates, but little is known about its specificity for antipsychotics. The objective of this study was to assess the affinity of some atypical antipsychotic drugs in vitro for P-gp as indicative of their potential as P-gp substrates in vivo. The activity of P-gp towards four atypical and two conventional antipsychotics and a proven substrate, verapamil, was examined by their P-gp ATPase activity, a putative measure of P-gp affinity. The Michaelis-Menten equation was fitted to the data. The rank order of the ratio V(max) / K(m) was: verapamil (2.6) > quetiapine (1.7) > risperidone (1.4) > olanzapine (0.8) > chlorpromzaine (0.7) > haloperidol (0.3) = clozapine (0.3). The atypical antipsychotics quetiapine and risperidone were relatively good P-gp substrates, although their affinities were not as high as verapamil. Olanzapine showed intermediate affinity and clozapine showed the least affinity of the drugs studied. These results suggest that P-gp is likely to influence the access to the brain of all of the atypical antipsychotics studied to various degrees. In vivo studies are needed to confirm these findings.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Chlorpromazine P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Clozapine P-glycoprotein 1 Protein Humans UnknownSubstrateDetails Haloperidol P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Olanzapine P-glycoprotein 1 Protein Humans NoSubstrateDetails Quetiapine P-glycoprotein 1 Protein Humans UnknownSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareRisperidoneVerapamil The serum concentration of Risperidone can be increased when it is combined with Verapamil.