radolmidine has been researched along with atipamezole* in 2 studies
2 other study(ies) available for radolmidine and atipamezole
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Regulation of neuropathic hypersensitivity by α(2) -adrenoceptors in the pontine A7 cell group.
Pontine A5, A6 (locus coeruleus) and A7 cell groups provide noradrenergic innervation of the spinal cord. Here, we assessed whether activation of α(2) -adrenoceptors in A7 influences peripheral nerve injury-induced hypersensitivity in the rat, and whether spinal α(2) -adrenoceptors mediate the descending effect. Fadolmidine, an α(2) -adrenoceptor agonist that because of its pharmacokinetic properties has a limited spread from the injection site, was microinjected through a chronic guide cannula into A7 or for comparison into A6 ipsilateral to the nerve injury. Moreover, atipamezole, an α(2) -adrenoceptor antagonist, was injected intrathecally in an attempt to reverse the possible antihypersensitivity effect. Tactile hypersensitivity was assessed in the injured limb by determining limb withdrawal evoked by calibrated monofilaments, mechanical hyperalgesia by determining withdrawal evoked by noxious mechanical stimulation of the paw, and thermal nociception by assessing heat-induced withdrawal of the intact tail. Fadolmidine (1.0 or 3.0 μg) in A7, but not in A6, produced a tactile antihypersensitivity effect. Intrathecal atipamezole (5 μg) reversed the tactile antihypersensitivity effect by fadolmidine in A7. Atipamezole alone (5.0 μg) intrathecally or in A7 failed to influence tactile hypersensitivity. Fadolmidine in A7 failed to influence mechanical hyperalgesia or heat nociception at doses that produced a tactile antihypersensitivity effect. We propose that tonic noradrenergic drive of A6 by A7 promotes neuropathic hypersensitivity by suppressing descending noradrenergic inhibition originating in A6. Consequently, the activation of inhibitory α(2) -adrenoceptors within the pontine A7 cell group suppresses neuropathic hypersensitivity by disinhibiting A6 and its descending noradrenergic pathways acting on spinal α(2) -adrenoceptors. Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Hyperalgesia; Imidazoles; Indans; Male; Microinjections; Neuralgia; Pain Measurement; Pons; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-2; Spinal Cord | 2013 |
Selective and segmentally restricted antinociception induced by MPV-2426, a novel alpha-2-adrenoceptor agonist, following intrathecal administration in the rat.
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.. 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.. 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.. 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. Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Analgesics; Animals; Dexmedetomidine; Electrophysiology; H-Reflex; Hot Temperature; Imidazoles; Immersion; Indans; Injections, Spinal; Male; Pain Measurement; Rats; Rats, Wistar | 2000 |