Effect of the centrally acting muscle relaxant tizanidine on spinal reflexes: involvement of descending noradrenergic systems.
Experiments were performed on intact and spinalized rats anesthetized with urethane and alpha-chloralose. In intact rats, administration of tizanidine (0.1 mg/kg, i.v.) decreased the mono- (MSR) and polysynaptic reflex potentials (PSR). Blood pressure was initially elevated and then lowered by tizanidine. Although pretreatments with hexamethonium and phentolamine prevented the tizanidine-induced decrease in blood pressure, the depressant effects of tizanidine on the reflexes remained. The alpha 2-antagonist idazoxan inhibited the tizanidine-induced decrease in spinal reflexes, suggesting that central alpha 2-adrenoceptors are involved in the depression of the reflexes. In spinalized rats, tizanidine transiently increased the MSR and gradually decreased the PSR. Blood pressure was elevated transiently by tizanidine. Although the hypertensive effect of tizanidine was inhibited by phentolamine, the effect of tizanidine on the PSR did not change. Prazosin blocked the stimulatory effect of tizanidine on the MSR and caused a rapid decrease of the PSR, suggesting that spinal alpha 1-adrenoceptors are involved in the enhancement of the reflexes. These results suggest that the depressant effects of tizanidine on spinal reflexes are due to the supraspinal and spinal effects of the drug, and not to changes in blood pressure.
Ono
H
H
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Fukushima
C
C
Fukuda
H
H
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003655:Decerebrate State / Q000503:physiopathology; D004146:Dioxanes / Q000494:pharmacology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D019329:Idazoxan; D008297:Male; D009125:Muscle Relaxants, Central / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D012018:Reflex / Q000187:drug effects*; D012023:Reflex, Monosynaptic / Q000187:drug effects; D013116:Spinal Cord / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D006584:Hexamethonium Compounds; D009125:Muscle Relaxants, Central; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; C023754:tizanidine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin; D019329:Idazoxan; D010646:Phentolamine