Effect of NE-100, a novel sigma receptor ligand, on phencyclidine-induced cognitive dysfunction.
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.
Ogawa
S
S
Department of Pharmacology, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Okuyama
S
S
Araki
H
H
Otomo
S
S
D000818:Animals; D000840:Anisoles / Q000378:metabolism / Q000494:pharmacology*; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D004347:Drug Interactions; D008024:Ligands; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology*; D005082:Physical Exertion / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011437:Propylamines / Q000378:metabolism / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects* / Q000378:metabolism; D016713:Ritanserin / Q000494:pharmacology*; D013550:Swimming
D000840:Anisoles; D014151:Anti-Anxiety Agents; D008024:Ligands; D010880:Piperidines; D011437:Propylamines; D011743:Pyrimidines; D017480:Receptors, sigma; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D016713:Ritanserin; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; C078773:DuP 734; D010622:Phencyclidine