α2-adrenoceptors and 5-HT receptors mediate the antinociceptive effect of new pyrazolines, but not of dipyrone

In this study, we investigated whether spinal noradrenergic and serotonergic systems are involved in the antinociception induced by the novel pyrazolines 3-methyl- and 3-phenyl-5-hydroxy-5-trichloromethyl-4,5-dihydro-1H-1-pyrazole-1-carboxyamide (MPCA and PPCA, respectively), and the pyrazolinone dipyrone in the acetic acid writhing (stretching) test in mice. Intrathecal (i.t.) administration of methysergide (3 and 10 mug) and yohimbine (3 mug), but not of prazosin (0.3 and I mug) prevented the antinociceptive action of MPCA and PPCA (500 mumol/kg, s.c.). Dipyrone-induced antinociception (500 mumol/kg, s.c.) was not affected by methysergide or adrenoceptor antagonists. These results suggest that spinal 5-HT receptors and alpha(2)-adrenoceptors are involved in the antinociception induced by MPCA and PPCA, but not in that elicited by dipyrone. (C) 2004 Elsevier B.V. All rights reserved.