MAZINDOL AND LIDOCAINE ARE ANTINOCICEPTIVES IN THE MOUSE FORMALIN MODEL - INVOLVEMENT OF DOPAMINE-RECEPTOR

The antinociceptive potential of mazindol, an anorectic drug, and lido caine, an amide-type local anesthetic, were investigated in the mouse formalin test with concurrent motor function assessment. In addition, the role of dopamine and opioid receptors in mediation of the antinoci ceptive action of these drugs was examined. The i.p. injection of mazi ndol (1.25-10 mg/kg) and lidocaine (10-30 mg/kg) induced significant a ntinociceptive responses in both phases of the test. Cocaine (20 mg/kg , i.p.), used as positive control, also inhibited the pain responses c aused by formalin. Haloperidol (0.2 mg/kg, i.p.), and sulpiride (5 mg/ kg, i.p.), a dopamine D-2 receptor antagonist, reduced the antinocicep tive actions of mazindol and cocaine, while SCH 23390, R(+)-7-chloro - hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine (0.03 mg /kg, i.p.), a dopamine D-2 receptor antagonist, did not affect these r esponses. Only the antinociception associated with mazindol was revers ed by naloxone (2 mg/kg, i.p.). The same pretreatments failed to modif y lidocaine-induced antinociception. The drug conditions used in this study did not reveal any motor impairment in the rotarod test. These o bservations suggest an involvement of dopaminergic mechanisms, mainly via dopamine D-2 receptors, in the antinociceptive action of mazindol in the formalin test, but the nature of mechanisms involved in the lid ocaine responses remains unsolved. (C) 1997 Elsevier Science B.V.