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  • Title: Association of the peptidase inhibitor RB 101 and a CCK-B antagonist strongly enhances antinociceptive responses.
    Author: Maldonado R, Derrien M, Noble F, Roques BP.
    Journal: Neuroreport; 1993 Jul; 4(7):947-50. PubMed ID: 8369487.
    Abstract:
    The brain peptide cholecystokinin (CCK) has been shown to counteract the analgesic effects of morphine suggesting a physiological antagonism between opioid and CCK neural systems. This has been definitely demonstrated in this study by co-administration of the CCK-B selective antagonist L-365,260 with RB 101, a systemically active inhibitor of peptidases, which fully protects the endogenous opioids, the enkephalins, from their inactivation. The naloxone reversible analgesic effects induced by RB 101 in the mouse hot-plate and rat tail-flick tests were strongly increased by low doses of L-365,260. These results could have important clinical applications by reducing the efficient dose of RB 101, which has recently been shown to be practically devoid of morphine-like side-effects.
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