Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat.
The alpha1A- and alpha1B-adrenoceptor affinity of the typical (chlorpromazine, haloperidol, pimozide, thioridazine and trifluoperazine) and atypical (clozapine, olanzapine, quetiapine, risperidone and sertindole) antipsychotics was determined by competition binding at alpha1A- and alpha1B-adrenoceptors in rat submaxillary gland and liver. Although all antipsychotics bound to both subtypes with relatively high affinity (K(i)s<74 nM), none were selective (>10-fold). Comparison with published dopamine D2 receptor affinities suggests that antipsychotic blockade of alpha1A- and/or alpha1B-adrenoceptors may contribute to the antipsychotic activity of all the atypical and several of the typical antipsychotics examined.
Cahir
Marie
M
Department of Mental Health, The Queen's University of Belfast, Whitla Medical Building, 97 Lisburn Rd., Belfast BT9 7BL, UK. m.cahir@qub.ac.uk
King
David J
DJ
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
C547715:Adra1a protein, rat; C547718:Adra1b protein, rat; D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D018340:Receptors, Adrenergic, alpha-1