Antipsychotics differ in their ability to internalise human dopamine D2S and human serotonin 5-HT1A receptors in HEK293 cells

European Journal of Pharmacology
Peter HeuslerDidier Cussac

Abstract

Antipsychotic drugs act preferentially via dopamine D(2) receptor blockade, but interaction with serotonin 5-HT(1A) receptors has attracted interest as additional target for antipsychotic treatment. As receptor internalisation is considered crucial for drug action, we tested the propensity of antipsychotics to internalise human (h)D(2S) receptors and h5-HT(1A) receptors. Agonist-induced internalisation of hemaglutinin (HA)-tagged hD(2S) and HA-h5-HT(1A) receptors expressed in HEK293 cells was increased by coexpression of G-protein coupled receptor kinase 2 and beta-arrestin2. At the HA-hD(2S) receptor, dopamine, quinpirole and bromocriptine behaved as full agonists, while S(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3PPP] and sarizotan were partial agonists. The typical antipsychotic, haloperidol, and the atypical compounds, olanzapine, nemonapride, ziprasidone and clozapine did not internalise HA-hD(2S) receptors, whereas aripiprazole potently internalised these receptors (>50% relative efficacy). Among antipsychotics with combined D(2)/5-HT(1A) properties, bifeprunox and (3-exo)-8-benzoyl-N-[[(2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo-[3.2.1]octane-3-methanamine (SSR181507) partially internalised...Continue Reading

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Citations

Aug 16, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Nicolas AznavourLaurent Descarries
Dec 4, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ningning GuoStephen Rayport
Jan 16, 2014·Neurobiology of Learning and Memory·Rudy Schreiber, Adrian Newman-Tancredi
Oct 25, 2011·Progress in Neuro-psychopharmacology & Biological Psychiatry·Luiz Eduardo Baggio SavioAngela T S Wyse
May 16, 2009·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Kelly Juliana SeibtCarla Denise Bonan
Oct 9, 2013·International Journal of Geriatric Psychiatry·Eileen B Sweeney, Brian A Lawlor
Oct 1, 2013·The International Journal of Neuropsychopharmacology·Kristoffer SahlholmPeter Århem
Jun 15, 2017·The Journal of Pharmacy and Pharmacology·Adrian Newman-TancrediDidier Cussac

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