Dopamine D2(High) receptors moderately elevated by sertindole.
Because long-term administration of antipsychotics can cause behavioral dopamine supersensitivity, this study examined whether the antipsychotic sertindole could elicit biochemical changes indicative of dopamine supersensitivity. In rats, behavioral dopamine supersensitivity is consistently associated with an increased proportion of dopamine receptors that have high affinity for dopamine, namely D2(High), in homogenized striata. Nine days of subcutaneously injected sertindole (1.25 mg/kg/day) increased the proportion of D2(High) receptors between 186% and 215%, although the total population of D2 receptors did not change. Although the findings suggest that rats or patients treated with sertindole might exhibit behavioral dopamine supersensitivity, the drug-induced increase in D2(High) receptors was less than that previously found with haloperidol.
Seeman
Philip
P
Department of Pharmacology, Medical Science Building, University of Toronto, Toronto, Ontario, Canada M5S 1A8. philip.seeman@utoronto.ca
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D004294:Domperidone / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006150:Guanine Nucleotides; D006220:Haloperidol / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D010078:Oxazines; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D006150:Guanine Nucleotides; D007093:Imidazoles; D007211:Indoles; D010078:Oxazines; D017448:Receptors, Dopamine D2; C042631:naxagolide; D004294:Domperidone; C066304:sertindole; D006220:Haloperidol