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Related Concept Videos

Antipsychotic Drugs: Typical and Atypical Agents01:21

Antipsychotic Drugs: Typical and Atypical Agents

Antipsychotic drugs are classified into first-generation (typical) drugs including phenothiazines; and second-generation (atypical) drugs. Chlorpromazine hydrochloride (Thorazine), a phenothiazine derivative, broadly impacts the central, autonomic, and endocrine systems. This drug, along with typical agents like haloperidol (Haldol), primarily works by antagonizing D2 receptors, thus reducing dopaminergic neurotransmission. However, typical antipsychotics can cause side effects such as sedation...
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The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
Psychosis and Antipsychotic Drugs: Overview01:28

Psychosis and Antipsychotic Drugs: Overview

The term "psychosis" refers to a spectrum of mental disorders characterized by abnormal thoughts, perceptions, and behaviors. It can manifest as mood disorders, dementia, delirium with psychotic features, substance-induced psychosis with psychotic features, brief psychotic disorder, delusional disorder, schizoaffective disorder, and schizophrenia. Among all these disorders, schizophrenia is the most common psychotic disorder, affecting 1% of the worldwide population. Psychotic symptoms in all...
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HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice
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Relationship between P-glycoprotein and second-generation antipsychotics.

Tim Moons1, Mariska de Roo, Stephan Claes

  • 1University Psychiatric Centre, Catholic University Leuven, Herestraat 49, 3000 Leuven, Belgium. tim.moons@uzleuven.be

Pharmacogenomics
|August 17, 2011
PubMed
Summary
This summary is machine-generated.

P-glycoprotein (P-gp) influences how individuals respond to antipsychotics. Many second-generation antipsychotics (SGAs) interact with P-gp, affecting drug concentrations and patient outcomes, though clinical results vary.

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Genetics

Background:

  • P-glycoprotein (P-gp) is a membrane transporter protein implicated in drug disposition.
  • Individual differences in P-gp function may explain variable responses to antipsychotic medications.
  • Second-generation antipsychotics (SGAs) are widely used in treating psychiatric disorders.

Purpose of the Study:

  • To review current knowledge on P-glycoprotein and its interactions with second-generation antipsychotics.
  • To identify which SGAs are substrates or inhibitors of P-gp.
  • To explore the clinical implications of P-gp variability in antipsychotic treatment.

Main Methods:

  • Systematic internet search for original research articles on P-gp and SGAs.
  • Analysis of identified studies regarding P-gp substrate and inhibitor status of SGAs.
  • Review of animal model and patient data on P-gp's role in antipsychotic efficacy and adverse effects.

Main Results:

  • Amisulpride, aripiprazole, olanzapine, perospirone, risperidone, and paliperidone are identified as P-gp substrates.
  • Clozapine and quetiapine are unlikely to be P-gp substrates.
  • Most antipsychotics inhibit P-gp, potentially altering plasma and brain concentrations of other substrates.

Conclusions:

  • P-gp plays a significant role in the pharmacokinetics and pharmacodynamics of several SGAs.
  • Genetic variations in P-gp may influence treatment outcomes, with decreased function potentially linked to better clinical performance.
  • Further research is needed to clarify P-gp's role in antipsychotic adverse effects and to account for confounding factors in patient studies.