Enhancement of the effects of a complete inhibitor of enkephalin-catabolizing enzymes, RB 101, by a cholecystokinin-B receptor antagonist in diabetic rats

British Journal of Pharmacology
M A Coudoré-CivialeA Eschalier

Abstract

1. RB 101, a complete inhibitor of enkephalin-catabolizing enzymes, has been previously shown to produce antinociception in normal rats after systemic administration. Moreover, its coadministration with a cholecystokinin-B (CCK-B) receptor antagonist has been shown to strongly enhance its antinociceptive effect in normal rats. In this work, we determined whether RB 101 was able to reduce hyperalgesia and allodynia in diabetic rats, a model of neuropathic pain. The type of opioid receptors (mu or delta) involved was determined using naloxone and naltrindole, respectively, and the interactions between endogenous enkephalins and CCK on nociception control was investigated using coadministration of RB 101 and the CCK-B receptor antagonist CI-988. 2. RB 101 suppressed mechanical hyperalgesia (paw pressure-induced vocalization test), partially alleviated mechanical allodynia (von Frey hair test), and was ineffective in thermal allodynia (tail immersion test). The analgesic effect was completely cancelled by naloxone or naltrindole, suggesting that is requires the availability of mu- and/or delta-opioid receptors. 3. The combination of an inactive dose of CI-988 with the lowest effective dose of RB 101 resulted in a stronger increase ...Continue Reading

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Citations

Jun 25, 2002·European Journal of Pharmacology·Jean-Michel BenoistDaniel Le Bars
Oct 12, 2002·Pharmacology, Biochemistry, and Behavior·L P RutledgeM G Kolta
Jan 22, 2003·Peptides·Richard J Bodnar, Maria M Hadjimarkou
Mar 31, 2012·Nature Reviews. Drug Discovery·Bernard P RoquesMichel Wurm
Jan 18, 2007·Expert Opinion on Therapeutic Targets·Florence Noble, Bernard P Roques
Jan 29, 2014·JAK-STAT·Melanie Busch-Dienstfertig, Sara González-Rodríguez
Aug 28, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anja SchreiterHalina Machelska
Sep 1, 2020·Expert Opinion on Pharmacotherapy·Shazli AzmiRayaz A Malik

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