title: Synthesis of (+)-cis-N-(4-isothiocyanatobenzyl)-N-normetazocine, an isothiocyanate derivative of N-benzylnormetazocine as acylant agent for the sigma(1) receptor.
abstract: (+)-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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy. ggrmedch@unict.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ronsisvalle
authors.forename: Orazio
authors.initials: O
authors.lastname: Prezzavento
authors.forename: Agostino
authors.initials: A
authors.lastname: Marrazzo
authors.forename: Franco
authors.initials: F
authors.lastname: Vittorio
authors.forename: Michele
authors.initials: M
authors.lastname: Massimino
authors.forename: Giovanna
authors.initials: G
authors.lastname: Murari
authors.forename: Santi
authors.initials: S
authors.lastname: Spampinato
mesh_terms: 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
chemical_list: C458046:N-(4-isothiocyanatobenzyl)-N-normetazocine; D017465:Receptors, Opioid, delta; C089049:N-benzylnormetazocine; D003496:Cyclazocine; D010423:Pentazocine