Typical antipsychotics exhibit inverse agonist activity at rat dopamine D1-like receptors expressed in Sf9 cells.
The baculovirus system has been used to express the rat dopamine D1 receptors in Spodoptera frugiperda (Sf9) cells. A panel of typical antipsychotics including, alpha-flupenthixol, fluphenazine and thioridizine were found to inhibit dopamine-dependent stimulation of adenylyl cyclase. However, these compounds were also found to inhibit adenylyl cyclase activity in the absence of agonist in Sf9 cells expressing dopamine D1-like receptors. Therefore, these nonselective dopamine receptor compounds displayed negative intrinsic or inverse agonist activity. None of the compounds tested were neutral antagonists.
Martin
M W
MW
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
Scott
A W
AW
Johnston
D E
DE
Griffin
S
S
Luedtke
R R
RR
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D016367:Baculoviridae / Q000235:genetics; D001667:Binding, Competitive; D002460:Cell Line; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D008024:Ligands; D011869:Radioligand Assay; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D050641:Receptors, Dopamine D5; D018411:Spodoptera
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; C493607:Drd5 protein, rat; D008024:Ligands; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; D000262:Adenylyl Cyclases; D004298:Dopamine