Possible involvement of noradrenergic descending pain-modulating pathways in the mode of antinociceptive action of flupirtine, a novel non-opioid analgesic.
These experimental studies were conducted to obtain information about the antinociceptive action of flupirtine within the central nervous system. Flupirtine dose-dependently increased pain threshold in the electrostimulated pain test in mice. Its antinociceptive activity was attenuated by simultaneous administration of the noradrenergic alpha 1/alpha 2-antagonist yohimbine and alpha 2-antagonist idazoxane. By contrast, the analgesia induced by codeine or morphine was not influenced by alpha 2-adrenergic antagonists at all. A striking resemblance could be observed in the pharmaco-EEG of freely moving rats treated with clonidine and flupirtine, respectively. The present results are consistent with the hypothesis that the noradrenergic descending pain-modulating system might be involved in the antinociceptive mode of action of flupirtine.
Nickel
B
B
Department of Pharmacology, ASTA Pharma AG, Frankfurt, Federal Republic of Germany.
Engel
J
J
Szelenyi
I
I
D000631:Aminopyridines / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004525:Efferent Pathways / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D000631:Aminopyridines; D000700:Analgesics; C034161:flupirtine; D009638:Norepinephrine