Discrimination of (+)-3-PPP sites from DTG sites by FH-510, a novel potent sigma ligand, in rat brain.
The effect of 5,8-dimethyl-4-(2-di-n-propylaminoethyl)carbazol monohydrochloride (FH-510) on the binding of sigma ligands such as [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ([3H](+)-3-PPP) and [3H]1,3-di-o-tolylguanidine ([3H]DTG) to rat brain membranes was studied. The inhibitory effect of FH-510 on [3H](+)-3-PPP binding to membranes of rat brain was 260 times more potent than that on [3H]DTG binding. Scatchard plot analysis showed that FH-510 inhibited [3H](+)-3-PPP binding in a competitive manner, while the inhibitory effect of FH-510 on [3H]DTG binding was noncompetitive. These results suggest that (+)-3-PPP sites could be discriminated from DTG sites, and that FH-510 binds preferentially to (+)-3-PPP recognition sites in rat brain.
Chaki
S
S
Department of Pharmacology, Taisho Pharmaceutical Co. Ltd., Saitama, Japan.
Tanaka
M
M
Muramatsu
M
M
Otomo
S
S
D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D015259:Dopamine Agents / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010880:Piperidines / Q000378:metabolism*; D011437:Propylamines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D002227:Carbazoles; D015259:Dopamine Agents; D006146:Guanidines; D010880:Piperidines; D011437:Propylamines; C083362:FH 510; C026539:preclamol; C050232:1,3-ditolylguanidine