Selective and segmentally restricted antinociception induced by MPV-2426, a novel alpha-2-adrenoceptor agonist, following intrathecal administration in the rat.
BACKGROUND
MPV-2426 (radolmidine) is a novel alpha-2-adrenoceptor agonist developed for spinal pain therapy. In the present study we determined the segmental distribution and selectivity of the antinociceptive effect induced by MPV-2426 following i.t. administration in rats.


METHODS
The experiments were performed in lightly anesthetized rats with an i.t. catheter for administration of drugs into the lumbar spinal cord level. To determine segmental distribution of antinociception, the withdrawal latency of the tail and forepaw from a hot water bath was measured. To determine selectivity of reflex modulation, the effect of i.t. MPV-2426 on the innocuous H-reflex was determined.


RESULTS
In the hot water immersion test MPV-2426 produced a dose-dependent (0.3-3.0 microg) prolongation of tail withdrawal latency whereas the effect on forepaw withdrawal latency was short of significance. Dexmedetomidine, the reference alpha-2-adrenoceptor agonist, produced a significant dose-related prolongation of both the tail and the forepaw withdrawal (0.3 and 1.0 microg). MPV-2426 (1.0 and 3.0 microg) produced no significant change in the amplitude of the H-reflex or M-response induced by electrical stimulation of the tibial nerve, nor any change in the modulation of the H-reflex amplitude induced by conditioning sural nerve stimulation. The antinociception induced by MPV-2426 was completely reversed by atipamezole (1 mg/kg s.c.), an alpha-2-adrenoceptor antagonist.


CONCLUSIONS
MPV-2426 produces a selective and segmentally more restricted antinociceptive effect than dexmedetomidine following i.t. administration. The antinoception induced by MPV-2426 is due to action on spinal alpha-2-adrenoceptors.
Onttonen
T
T
Department of Physiology, Institute of Biomedicine, University of Helsinki, Finland.
Kalmari
J
J
Pertovaara
A
A
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology; D004594:Electrophysiology; D006181:H-Reflex / Q000187:drug effects; D006358:Hot Temperature; D007093:Imidazoles / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007101:Immersion; D007189:Indans / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D007093:Imidazoles; D007189:Indans; C050701:atipamezole; D020927:Dexmedetomidine; C400294:radolmidine