title: GBR-12909 and fluspirilene potently inhibited binding of [3H] (+)3-PPP to sigma receptors in rat brain.
abstract: Fluspirilene and GBR-12909, two compounds structurally similar to BMY-14802 and haloperidol, were assessed for their ability to interact with sigma receptors. Fluspirilene, an antipsychotic agent that interacts potently with dopamine receptors, inhibited the binding of [3H]-(+) 3-PPP (IC50 = 380 nM) more potently than rimcazole, a putative sigma antagonist that was tested clinically for antipsychotic activity. GBR-12909, a potent dopamine uptake blocker, also inhibited the binding of [3H]-(+) 3-PPP with an IC50 of 48 nM. However, other compounds that block the re-uptake of catecholamines, such as nomifensine, desipramine, imipramine, xylamine, benztropine and cocaine, were much weaker than GBR-12909 as sigma ligands. Thus, GBR-12909 and fluspirilene, compounds structurally similar to BMY-14802, are potent sigma ligands.
authors.affiliation: CNSDR, G. D. Searle & Co., Chesterfield, MO 63198.
authors.forename: P C
authors.initials: PC
authors.lastname: Contreras
authors.forename: M E
authors.initials: ME
authors.lastname: Bremer
authors.forename: T S
authors.initials: TS
authors.lastname: Rao
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism*; D005484:Fluspirilene / Q000494:pharmacology*; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D010880:Piperidines / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017480:Receptors, sigma
chemical_list: D014150:Antipsychotic Agents; D015259:Dopamine Agents; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D010880:Piperidines; D011957:Receptors, Opioid; D017480:Receptors, sigma; C043425:vanoxerine; C026539:preclamol; D005484:Fluspirilene