Evidence for an anti-amnesic effect of JO 1784 in the rat: a potent and selective ligand for the sigma receptor.

Abstract

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.

• Authors: B Earley, M Burke, B E Leonard, C J Gouret, J L Junien
• Journal: Brain research (Brain Res) Vol. 546 Issue 2 Pg. 282-6 (Apr 19 1991) ISSN: 0006-8993 [Print] Netherlands
• PMID: 1676927 (Publication Type: Journal Article)

Chemical References

• Antipsychotic Agents
• Carbazoles
• Cinnamates
• Cyclopropanes
• Dopamine Agents
• Guanidines
• Ligands
• Piperidines
• Receptors, Opioid
• Receptors, sigma
• SK&F 10047
• preclamol
• rimcazole
• Scopolamine
• Phenazocine
• 1,3-ditolylguanidine
• igmesine

Topics

• Amnesia (chemically induced, prevention & control)
• Animals
• Antipsychotic Agents (pharmacology)
• Avoidance Learning (drug effects)
• Behavior, Animal (drug effects)
• Carbazoles (pharmacology)
• Cinnamates (pharmacology)
• Cyclopropanes (pharmacology)
• Dopamine Agents (pharmacology)
• Dose-Response Relationship, Drug
• Guanidines (pharmacology)
• Ligands
• Male
• Phenazocine (analogs & derivatives, pharmacology)
• Piperidines (pharmacology)
• Rats
• Rats, Inbred Strains
• Receptors, Opioid (drug effects)
• Receptors, sigma
• Scopolamine