Evidence for an anti-amnesic effect of JO 1784 in the rat: a potent and selective ligand for the sigma receptor.
JO 1784 ((+)-N-Cyclopropyl-methyl-N-methyl-1,4-diphenyl-1-yl-but-3-en-1-ylami ne, hydrochloride), has been recently described as a selective ligand for the sigma receptor with an IC50 of 39 +/- 8 nM28. In the present study the effects of JO 1784 on experimental induced amnesia were investigated using one trial passive avoidance task in rats. Amnesia was produced by injecting scopolamine (1 mg/kg i.p.) 30 min before the second session (T2) on day 2 of the passive avoidance task. The anti-amnesic effect of JO 1784 was compared with other typical and atypical psychotropic drugs which interact at the sigma and or the phencyclidine site. JO 1784 was studied at 5 doses; 0.0625, 0.25, 1.0, 4.0 and 16.0 mg/kg i.p. ((+)-3-(3-hydroxyphenyl)-N-1-(propyl)piperidine ((+)-3-PPP). Rimcazole, (+)-N-allylnormetazocine ((+)-NANM), 1,3-di(2-tolyl) guanidine (DTG) were studied at 4 doses; 0.25, 1.0, 4.0 and 8.0 mg/kg i.p. All drugs were administered 60 min before the test (T2) on day 2 i.e. 30 min before scopolamine. Piracetam (1000 mg/kg p.o.) administered in the same test conditions was used as a reference compound in each experiment. Of the drugs investigated JO 1784 (0.25, 1.0, 4.0 and 16.0 mg/kg i.p.), (+)-3-PPP (0.25, 1.0 and 4.0 mg/kg i.p.), DTG (1.0, 4.0 and 8.0 mg/kg) and piracetam significantly reversed scopolamine induced amnesia on day 3 (T3). At the lower dose, JO 1784 (0.0625 mg/kg) failed to reverse the amnesic effects of scopolamine on day 3. These results suggest that JO 1784 the selective sigma ligand, may be beneficial in amnesic status.
Pharmacology Department, University College, Galway, Ireland.
B
B
Earley
M
M
Burke
B E
BE
Leonard
C J
CJ
Gouret
J L
JL
Junien
D000647:Amnesia / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology; D008024:Ligands; D008297:Male; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017480:Receptors, sigma; D012601:Scopolamine
D014150:Antipsychotic Agents; D002227:Carbazoles; D002934:Cinnamates; D003521:Cyclopropanes; D015259:Dopamine Agents; D006146:Guanidines; D008024:Ligands; D010880:Piperidines; D011957:Receptors, Opioid; D017480:Receptors, sigma; C012134:SK&F 10047; C026539:preclamol; C034931:rimcazole; D012601:Scopolamine; D010620:Phenazocine; C050232:1,3-ditolylguanidine; C065310:igmesine