Antinociceptive activity of salsolinol (racemate, R(+)-, S(-)-enantiomers): evidence of a peripheral mechanism.
The existence and the characteristics of the antinociceptive action of salsolinol (racemate) and its two R(+)- and S(-)-enantiomers were studied using different pain tests in mice. None of these drugs possessed a significant activity on the tests sensitive to central acting analgesics (hot-plate and tail-flick tests), either after systemic (i.p.) or central (i.c.v.) injections. However, injected i.p., they reduced the number of writhes induced by phenylbenzoquinone; the ED50 was 79 +/- 2, 73 +/- 2 and 61 +/- 2 mg/kg for racemate, R(+)- and S(-)-enantiomer respectively. This activity was not antagonized by naloxone. Moreover, racemate and S(-) reduced, only for the highest used active dose on the PBQ test (128 mg/kg, i.p.), the edema induced by an intraplantar injection of carrageenin. These results provide evidence of an analgesic activity independent of the endogenous opiate systems and involving a peripheral mechanism.
Laboratoire de Pharmacologie Médicale, INSERM U195, Faculté de Médecine, Clermont-Ferrand, France.
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A
Eschalier
F
F
Durif
J
J
Fialip
O
O
Aumaitre
H
H
Marty
G
G
Dordain
D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010146:Pain / Q000503:physiopathology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000700:Analgesics; D007546:Isoquinolines; C036617:salsolinol