Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
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Involvement of Supraspinal Imidazoline Receptors and Descending Monoaminergic Pathways in Tizanidine-Induced Inhibition of Rat Spinal Reflexes
Yurika KinoMitsuo TanabeMotoko HondaHideki Ono
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2005 Volume 99 Issue 1 Pages 52-60

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Abstract

The neuronal pathways involved in the muscle relaxant effect of tizanidine were examined by measurement of spinal reflexes in rats. Tizanidine (i.v. and intra-4th ventricular injection) decreased the mono- and disynaptic (the fastest polysynaptic) reflexes (MSR and DSR, respectively) in non-spinalized rats. Depletion of central noradrenaline by 6-hydroxydopamine abolished the depressant effect of tizanidine on the MSR almost completely and attenuated the effect on the DSR. Co-depletion of serotonin by 5,6-dihydroxytryptamine and noradrenaline resulted in more prominent attenuation of tizanidine-induced inhibition of the DSR. Supraspinal receptors were then studied using yohimbine- and some imidazoline-receptor ligands containing an imidazoline moiety. Idazoxan (I1, I2, I3, and α2), efaroxan (I1, I3, and α2), and RX821002 (I3 and α2), but not yohimbine, an α2-adrenergic receptor antagonist with no affinity for I receptors, antagonized the inhibitory effects of tizanidine. Thus, supraspinal I receptors (most likely I3) and descending monoaminergic influences are necessary for tizanidine-induced inhibition of spinal segmental reflexes.

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© The Japanese Pharmacological Society 2005
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