Evidence of the involvement of dopamine in the analgesic effect of nefopam.
The involvement of brain monoamines in the mechanism of action of nefopam, a new analgesic, was investigated in rats. The study was designed to evaluate the effect of various means of impairing monoaminergic transmission on nefopam analgesia as measured with the hot plate method. Pretreatment with reserpine (2 mg/kg) significantly reduced the antinociceptive action of nefopam (40 mg/kg), indicating that the interaction of this drug with the monoaminergic systems is important for its effects. A role for serotonin (5-HT) or norepinephrine (NE) was ruled out by the fact that selective depletion of 5-HT (using 5,7-dihydroxytryptamine) or NE (using DSP-4 or FLA-63) did not affect nefopam analgesia. A significant reduction of the effect of nefopam was found in rats pretreated with 6-hydroxydopamine (6-OHDA). Also 6-OHDA plus desipramine, which selectively depleted brain DA, markedly reduced the antinociceptive effect of nefopam. The data strongly suggest that a critical dopaminergic synapse is involved in the mechanism by which nefopam inhibits nociceptive responses in rats.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000700:Analgesics; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000502:physiology; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D006892:Hydroxydopamines / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009340:Nefopam / Q000494:pharmacology*; D010079:Oxazocines / Q000494:pharmacology*; D016627:Oxidopamine; D051381:Rats; D012110:Reserpine / Q000494:pharmacology
D000700:Analgesics; D001596:Benzylamines; D002395:Catecholamines; D006892:Hydroxydopamines; D010079:Oxazocines; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D015116:5,7-Dihydroxytryptamine; D009340:Nefopam; D012110:Reserpine; D016627:Oxidopamine; C012102:DSP 4; D003891:Desipramine; D004298:Dopamine