Differential pharmacological regulation of drug efflux and pharmacoresistant schizophrenia

BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology
Mary Bebawy, Manoranjenni Chetty

Abstract

Pharmacoresistant schizophrenia is a significant impediment to the successful management of the disease. The expression and function of P-glycoprotein (P-gp) has recently been implicated in this phenomenon. P-gp is a multidrug efflux transporter that prevents drug substrates from crossing the blood-brain barrier (BBB). Although the direct interaction between individual antipsychotic agents and P-gp has been demonstrated, the effect of antipsychotic drug combinations used in disease management on P-gp transport function remains to be elucidated. This could have important clinical implications in some individuals as dosage adjustments based on plasma drug concentration changes may not always be appropriate if drug-drug interactions and the resulting changes in drug concentration in the brain are not considered. This paper introduces the potential impact that combination antipsychotic therapy may have on P-gp function at the BBB and discusses the consequences of this in the prevention and circumvention of unfavourable therapeutic response in schizophrenic disorders.

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Citations

Apr 19, 2011·Molecular Biology and Evolution·Andrea Blanquer, Maria-J Uriz
Mar 3, 2011·Journal of Clinical Psychopharmacology·Fayçal MouaffakAmine Benyamina
Dec 8, 2009·Neuroscience Letters·Winfried NeuhausChristian R Noe
May 17, 2011·Progress in Neuro-psychopharmacology & Biological Psychiatry·Alessandra MinelliLuisella Bocchio-Chiavetto
Apr 4, 2018·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Wenhuan XiaoXiaobin Zhang
Feb 5, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Richard CallaghanMary Bebawy
Jul 31, 2021·World Journal of Psychiatry·Matej ĽuptákJana Hroudová

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