Effect of NE-100, a novel sigma receptor ligand, on phencyclidine-induced cognitive dysfunction.

Abstract

N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) is a selective and potent sigma receptor ligand. We investigated the effects of NE-100 on phencyclidine (PCP)-induced cognitive dysfunction in rats in a water maze task. NE-100 significantly shortened the PCP-induced prolonged swimming latency as did 1-(cyclopropylmethyl)-4-[2'(4"-fluorophenyl)-2'-oxoethyl]- piperidine monohydrobromide (Dup 734), 4-[2'-(4"-cyanophenyl)-2'-oxoethyl]-1-(cyclopropyl-methyl)pi peridine (XJ 448), alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY 14802) and rimcazole, all of which are sigma receptor ligands and possibly antagonists. Ritanserin, a 5-HT2 receptor antagonist, also showed a tendency to shorten swimming latencies. Latencies of haloperidol-, cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-2-methoxy-5-chloro-4-met hyl- aminobenzamide (YM-09151-2)- and sulpiride-, dopamine D2 receptor antagonists, treated groups did not differ from that seen in the PCP-treated group. Thus, PCP-induced cognitive dysfunction may be improved by sigma receptor ligands.