Synthesis of (+)-cis-N-(4-isothiocyanatobenzyl)-N-normetazocine, an isothiocyanate derivative of N-benzylnormetazocine as acylant agent for the sigma(1) receptor.
(+)-cis-N-(4-Isothiocyanatobenzyl)-N-normetazocine (BNIT) (+)-(4) was designed and synthesized as a derivative of the potent and selective sigma(1) receptor ligand (+)-cis-N-benzyl-N-normetazocine for irreversibly blocking sigma(1) binding sites. Pretreatment of guinea pig brain membranes with BNIT (0.1, 1, and 5 microM) caused a concentration-dependent loss of binding of the selective sigma(1) ligand [(3)H]-(+)-pentazocine. Binding experiments with [(3)H]-1,3-di(2-tolyl)guanidine ([(3)H]-DTG), a ligand of sigma(1) and sigma(2) receptors, showed that pretreatment with BNIT blocked only the sigma(1) component of [(3)H]-DTG binding.
Ronsisvalle
Giuseppe
G
Department of Pharmaceutical Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy. ggrmedch@unict.it
Prezzavento
Orazio
O
Marrazzo
Agostino
A
Vittorio
Franco
F
Massimino
Michele
M
Murari
Giovanna
G
Spampinato
Santi
S
D000215:Acylation; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D010423:Pentazocine / Q000378:metabolism; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism
C458046:N-(4-isothiocyanatobenzyl)-N-normetazocine; D017465:Receptors, Opioid, delta; C089049:N-benzylnormetazocine; D003496:Cyclazocine; D010423:Pentazocine