Typical antipsychotics exhibit inverse agonist activity at rat dopamine D1-like receptors expressed in Sf9 cells

• Published in: European journal of pharmacology Vol. 420; no. 2; pp. 73 - 82
• Main Authors: Martin, Michael W, Scott, Allelia W, Johnston, Douglas E, Griffin, Suzy, Luedtke, Robert R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.05.2001; Elsevier
• Subjects: Adenylyl cyclase stimulation; Adenylyl Cyclases - drug effects; Adenylyl Cyclases - metabolism; Animals; Antipsychotic Agents - pharmacology; Antipyschotic; Baculoviridae - genetics; Baculovirus expression; Binding, Competitive; Biological and medical sciences; Cell Line; Dopamine - pharmacology; Dopamine Agonists - pharmacology; Dopamine D1 receptor; Dopamine receptor; Dose-Response Relationship, Drug; Gene Expression; Genetic Vectors - genetics; Inverse agonist; Ligands; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Radioligand Assay; Rats; Receptors, Dopamine D1 - agonists; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D1 - physiology; Receptors, Dopamine D5; Spodoptera; Baculovirus expression; Dopamine D1 receptor; Dopamine receptor; Inverse agonist; Adenylyl cyclase stimulation; Antipyschotic; Rat; Enzyme; Neuroleptic; Psychotropic; Rodentia; D1 Dopamine receptor; Phosphorus-oxygen lyases; Lyases; Gene expression; In vitro; Biological activity; Adenylate cyclase; Vertebrata; Mammalia; Animal; Established cell line; Models; Recombinant protein; Mechanism of action; Comparative study
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)00982-7

The baculovirus system has been used to express the rat dopamine D1 receptors in Spodoptera frugiperda (Sf9) cells. A panel of typical antipsychotics including, α-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.