Study of the antinociceptive effect of tetrahydropapaveroline derivatives. Interaction with opioids
| Autor: | J. Fialip, F Durif, Philippe Dostert, F Bétoin, G. Dordain, Alain Eschalier |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Analgesics Morphine Naloxone Chemistry Tetrahydropapaveroline Drug Synergism Stereoisomerism Long-term potentiation General Medicine (+)-Naloxone Pharmacology General Biochemistry Genetics and Molecular Biology Mice Nociception medicine Animals Analgesia General Pharmacology Toxicology and Pharmaceutics Enantiomer ED50 Endogenous opioid medicine.drug |
| Zdroj: | Life Sciences. 59:PL133-PL139 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/0024-3205(96)00394-3 |
| Popis: | The antinociceptive effect of racemic tetrahydropapaveroline (THP), of its two R(+)- and S(-) enantiomers, of 1-2-dehydro-THP and of 1-carboxy-THP was assessed using different pain tests in mice. None of these drugs possessed a significant activity in the hot-plate and tail-flick tests. However, after i.p. injection, they reduced the number of abdominal writhes induced by phenylbenzoquinone, with ED50 values of 51 +/- 7, 73 +/- 9 and 79 +/- 7 mg/kg for the most potent compounds: 1,2-dehydro-THP, +/- THP and -THP, respectively. This activity was not antagonized by naloxone (1 mg/kg, s.c.). However combination of inactive doses of these three compounds (32 mg/kg, i.p.) and of morphine (0.5 mg/kg, s.c.) led to a significant antinociceptive effect (83 to 85% of reduction of the number of writhes). This synergistic potentiation confirmed with the combination of +/- THP (16 mg/kg, i.p.) and morphine (0.5 mg/kg, s.c.) was totally inhibited by naloxone (1 mg/kg, s.c.). These results, although excluding a direct agonistic effect of THP derivatives on opiate receptors, suggest an indirect interaction of these drugs with the endogenous opioid system. |
| Databáze: | OpenAIRE |
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