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Differential effects of the novel analgesic, S 12813-4, on the spinal release of substance P- and calcitonin gene-related peptide-like materials in the rat

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Abstract

The possible inhibitory control by the novel analgesic S 12813-4 (3-(2-(4-phenylpiperazine-1-yl)-ethyl)2-oxo-2,3-dihydrooxazolo(b)pyridine) of spinal neurones containing substance P (SP) and/or calcitonin generelated peptide (CGRP) was assessed in vitro and in vivo in the rat. S 12813-4 (10 nM - 0.1 mM) did not affect the spinal release of CGRP-like material (CGRPLM) but inhibited in a concentration dependent manner the K+-evoked overflow of SP-like material (SPLM) from slices of the dorsal half of the rat lumbar enlargement. The inhibitory effect of 10 μM S 12813-4 on SPLM release was not additive with that of Na (0.1 mM), and could be prevented by the α2-adrenoceptor antagonist idazoxan (10 μM). Similarly, idazoxan (10 μM) suppressed the inhibition by intrathecally administered S 12813-4 (10 μM) of the spinal outflow of SPLM in halothane anaesthetized rats whose intrathecal space was perfused with an artificial cerebrospinal fluid. These data suggest that the analgesic effect of S 12813-4 might involve some α2-adrenoreceptor-mediated control of SPLM release within the spinal cord. Whether this control concerns SP-containing primary afferent fibres (presynaptic inhibition) or SP-containing interneurones and/or bulbo-spinal SP-ergic pathways (postsynaptic inhibition) deserves further investigations.

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Authors and Affiliations

  1. INSERM U. 288, Neurobiologie Cellulaire et Fonctionelle, Faculté de Médecine, Boulevard de l’Hôpital, Pitié-Salpêtrière, 91, F-75634, Paris Cedex 13, France

    E. Collin, D. Frechilla, M. Pohl, S. Bourgoin, A. Mauborgne, M. Hamon & F. Cesselin

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  1. E. Collin
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  2. D. Frechilla
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  3. M. Pohl
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  4. S. Bourgoin
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  5. A. Mauborgne
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  6. M. Hamon
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  7. F. Cesselin
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Correspondence to: E. Collin at the above address

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Collin, E., Frechilla, D., Pohl, M. et al. Differential effects of the novel analgesic, S 12813-4, on the spinal release of substance P- and calcitonin gene-related peptide-like materials in the rat. Naunyn-Schmiedeberg’s Arch Pharmacol 349, 387–393 (1994). https://doi.org/10.1007/BF00170885

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  • DOI: https://doi.org/10.1007/BF00170885

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