Mode of antinociceptive action of flupirtine in the rat
Article first published online: 19 JUL 2012
1989 British Pharmacological Society
British Journal of Pharmacology
Volume 97, Issue 3, pages 835–842, July 1989
How to Cite
Szelenyi, I., Nickel, B., Borbe, H.O. and Brune, K. (1989), Mode of antinociceptive action of flupirtine in the rat. British Journal of Pharmacology, 97: 835–842. doi: 10.1111/j.1476-5381.1989.tb12023.x
- Issue published online: 19 JUL 2012
- Article first published online: 19 JUL 2012
- Received June 7, 1988, Revised January 25, 1989, Accepted February 8, 1989
- 1Flupirtine is a novel, centrally acting, non-opioid analgesic agent. The present investigation was undertaken to ascertain which neuronal systems might be responsible for its antinociceptive effect in rodents. The antinociceptive responses to the test compounds were examined in the tail-flick test.
- 2The selective destruction of noradrenergic pathways by 6-hydroxydopamine considerably reduced the flupirtine-induced inhibition of nociceptive responses but not the clonidine-induced antinociception which was significantly enhanced. Depletion of spinal 5-hydroxytryptaminergic pathways by pretreatment with 5,7-dihydroxytryptamine failed to affect the action of flupirtine and clonidine.
- 3The depletion of neurotransmitters by reserpine totally abolished the antinociceptive action of flupirtine. By contrast, clonidine-induced inhibition of nociceptive responses remained unchanged.
- 4Inhibition of the synthesis of noradrenaline by α-methyl-L-p-tyrosine attenuated the antinociception induced by flupirtine. In contrast, inhibition of the synthesis of 5-hydroxytryptamine by (±)−6-fluorotryptophan did not influence the antinociceptive activity of flupirtine.
- 5Inhibition of noradrenaline uptake by imipramine led to a significant augmentation of flupirtine-induced antinociception.
- 6Selective antagonists at α-adrenoceptors significantly decreased the antinociceptive action of flupirtine. Antinociception induced by clonidine was significantly diminished by idazoxan but not by prazosin.
- 7The 5-hydroxytryptamine (5-HT) antagonist, ketanserin diminished the antinociceptive activity of flupirtine, probably due to its additional α1-adrenoceptor antagonist activity. The antinociceptive effect of clonidine was not influenced by ketanserin.
- 8Cholinoceptor antagonists such as mecamylamine and pirenzepine did not alter the antinociceptive action of flupirtine. Flupirtine-induced antinociception also remained unchanged after pretreatment with haloperidol.
- 9Flupirtine has no pharmacologically relevant affinity for α1-, α2-adrenoceptors, 5-HT1- and 5-HT2-receptors as shown in direct binding studies.
- 10The present results indicate that the antinociceptive action induced by flupirtine depends on the descending noradrenergic pain-modulating system.