Alpha 2-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 microg) and yohimbine (3 microg), but not of prazosin (0.3 and 1 microg) prevented the antinociceptive action of MPCA and PPCA (500 micromol/kg, s.c.). Dipyrone-induced antinociception (500 micromol/kg, s.c.) was not affected by methysergide or adrenoceptor antagonists. These results suggest that spinal 5-HT receptors and alpha2-adrenoceptors are involved in the antinociception induced by MPCA and PPCA, but not in that elicited by dipyrone.