In vivo evaluation of (+)-MR200 as a new selective sigma ligand modulating MOP, DOP and KOP supraspinal analgesia

The compound (+)-MR200 [(+)-methyl (1R,2S)-2-{[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]methyl}-1-phenylcyclopropanecarboxylate] is a sigma ligand with increased affinity and selectivity compared to the structurally related ligand haloperidol. From the results of a previous study on the modulation...

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Bibliographic Details
Published in:Life sciences (1973) 2006-04, Vol.78 (21), p.2449-2453
Main Authors: Marrazzo, Agostino, Parenti, Carmela, Scavo, Valentina, Ronsisvalle, Simone, Maria Scoto, Giovanna, Ronsisvalle, Giuseppe
Format: Article
Language:English
Subjects:
(+)-MR200
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer - pharmacology
Analgesia
Analgesics, Opioid - pharmacology
Animals
Cyclopropanes - pharmacology
Enkephalin, Ala-MePhe-Gly- - pharmacology
Enkephalin, D-Penicillamine (2,5)- - pharmacology
Injections, Intraventricular
Male
Opioids
Pain Measurement - drug effects
Piperidines - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Opioid, delta - drug effects
Receptors, Opioid, kappa - drug effects
Receptors, Opioid, mu - drug effects
Receptors, sigma - drug effects
Sigma
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Summary:The compound (+)-MR200 [(+)-methyl (1R,2S)-2-{[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]methyl}-1-phenylcyclopropanecarboxylate] is a sigma ligand with increased affinity and selectivity compared to the structurally related ligand haloperidol. From the results of a previous study on the modulation of a systemically injected KOP opioid agonist analgesia by (+)-MR200, we analysed the influence of this sigma ligand on the antinociceptive effect of centrally injected MOP, DOP, and KOP selective agonists using the tail-flick test in rats. The results obtained confirmed that systemic administration of (+)-MR200 (1mg/Kg s.c.) did not modify basal tail-flick latency. Pre-treatment with 1mg/Kg s.c. of (+)-MR200 provided a significant increase in the antinociceptive effect of DAMGO (100ng/rat i.c.v.) and DPDPE (20 μg/rat i.c.v.). Conversely to previous reports, pre-treatment with (+)-MR200 reversed, in these experimental conditions, U-50488H (100μg/rat i.c.v.) analgesia. The mechanism involved in these effects was not clear, but provided additional data on a diverging modulator role of selective sigma-1 antagonists on KOP analgesia.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2005.10.005