Effect of flupirtine maleate on the nociceptive pathway, EEG, evoked potentials and polysynaptic reflexes in laboratory animals.
Flupirtine maleate (3, 6 and 10 mg/kg, i.v.) elevated the pain threshold following electrical stimulation of rabbit tooth pulp with a peak effect at 10 minutes, suggesting central analgesic activity. Codeine (1, 3 and 6 mg/kg, i.v.), but not zomepirac (3, 6 and 10 mg/kg, i.v.), was also effective. In the cat, electrical stimulation of the tooth pulp or the contralateral sciatic nerve (central and peripheral nociceptive pathways, respectively) results in evoked potentials (activation) in the midbrain (MRF), thalamus (VPL) and sensory cortex. Flupirtine maleate (1 mg/kg, i.v.) did not alter the evoked responses. But at 3 and 6 mg/kg, i.v. it effectively blocked activation in the MRF, VPL and sensory cortex, primarily following tooth pulp stimulation rather than after sciatic nerve stimulation, suggesting that flupirtine was a selective antagonist of the central nociceptive pathway. Furthermore, in the cat, flupirtine at 3 mg/kg, i.v. blocked cortical and hippocampal arousal (activation) following MRF stimulation. At 6 and 10 mg/kg it partially antagonized the linguomandibular reflex (central polysynaptic reflex) but had little or no effect on the flexor reflex (peripheral polysynaptic reflex). The results of these investigations demonstrate the central nervous system activity of flupirtine maleate.
Gordon
R
R
Department of Pharmacology, Wallace Laboratories, Div. of Carter-Wallace, Inc., Cranbury, New Jersey 08512.
Sofia
R D
RD
Diamantis
W
W
D000631:Aminopyridines / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects*; D004569:Electroencephalography; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D008297:Male; D009434:Neural Pathways / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement / Q000379:methods; D011817:Rabbits; D012018:Reflex / Q000187:drug effects
D000631:Aminopyridines; D000700:Analgesics; C034161:flupirtine