Mazindol and lidocaine are antinociceptives in the mouse formalin model: involvement of dopamine receptor.
The antinociceptive potential of mazindol, an anorectic drug, and lidocaine, 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 antinociceptive action of these drugs was examined. The i.p. injection of mazindol (1.25-10 mg/kg) and lidocaine (10-30 mg/kg) induced significant antinociceptive responses in both phases of the test. Cocaine (20 mg/kg, i.p.), used as positive control, also inhibited the pain responses caused by formalin. Haloperidol (0.2 mg/kg, i.p.), and sulpiride (5 mg/kg, i.p.), a dopamine D2 receptor antagonist, reduced the antinociceptive actions of mazindol and cocaine, while SCH 23390, R(+)-7-chloro 8-hydroxy-3methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine (0.03 mg/kg, i.p.), a dopamine D1 receptor antagonist, did not affect these responses. Only the antinociception associated with mazindol was reversed by naloxone (2 mg/kg, i.p.). The same pretreatments failed to modify lidocaine-induced antinociception. The drug conditions used in this study did not reveal any motor impairment in the rotarod test. These observations suggest an involvement of dopaminergic mechanisms, mainly via dopamine D2 receptors, in the antinociceptive action of mazindol in the formalin test, but the nature of mechanisms involved in the lidocaine responses remains unsolved.
Bittencourt
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AL
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianopolis SC, Brazil.
Takahashi
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RN
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D008454:Mazindol / Q000494:pharmacology*; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology
D000779:Anesthetics, Local; D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D009270:Naloxone; D008012:Lidocaine; D008454:Mazindol; D003042:Cocaine; D006220:Haloperidol