title: Involvement of imidazoline receptors in the centrally acting muscle-relaxant effects of tizanidine.
abstract: The centrally acting muscle relaxant tizanidine has an imidazoline structure and binds not only to alpha(2)-adrenoceptors but also to imidazoline receptors. The role of imidazoline receptors in the muscle-relaxant effect of tizanidine was studied using the alpha(2)-adrenoceptor/imidazoline receptor antagonist idazoxan and the alpha(2)-adrenoceptor antagonist yohimbine. Tizanidine decreased the spinal mono- and polysynaptic reflexes in intact rats, and the inhibitory effects were antagonized by idazoxan but not by yohimbine. After pretreatment with prazosin, tizanidine decreased the mono- and polysynaptic reflexes in spinalized rats. While yohimbine partly inhibited tizanidine-induced depression of the polysynaptic reflex, idazoxan completely abolished tizanidine-induced depression of spinal reflexes. Furthermore, tizanidine-induced muscle relaxation in the traction test was significantly inhibited by idazoxan but not by yohimbine. From these results, it is suggested that imidazoline receptors, but not alpha(2)-adrenoceptors, are involved in the supraspinal inhibitory effects of tizanidine on spinal reflexes, and at the spinal level, alpha(2)-adrenoceptors and imidazoline receptors are involved in the inhibitory effects of tizanidine.
authors.affiliation: Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Honda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sekiguchi
authors.forename: Naoko
authors.initials: N
authors.lastname: Sato
authors.forename: Hideki
authors.initials: H
authors.lastname: Ono
mesh_terms: D000818:Animals; D002574:Cervical Vertebrae; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D054755:Imidazoline Receptors; D008297:Male; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000502:physiology*; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries
chemical_list: D054755:Imidazoline Receptors; D009125:Muscle Relaxants, Central; D011955:Receptors, Drug; C023754:tizanidine; D003000:Clonidine