title: Intrathecal alpha2 adrenoceptor agonist clonidine inhibits mechanical transmission in mouse spinal cord via activation of muscarinic M1 receptors.
abstract: We examined the role of the spinal muscarinic receptor subtype in the anti-nociceptive effect of intrathecal (i.t.) alpha2 adrenoceptor agonist clonidine in mice. I.t. injection of the muscarinic receptor antagonist atropine completely inhibited i.t. clonidine-induced increase in the mechanical threshold, but did not affect the increase in tail-flick latency induced by i.t. clonidine. The clonidine-induced increase in mechanical threshold was inhibited by i.t. injection of the M1 receptor antagonist pirenzepine in a dose-dependent manner, and by the M3 receptor antagonist 4-DAMP, but not by the M2 receptor antagonist methoctramine. The potency of pirenzepine was greater than that of 4-DAMP. These results suggest that the clonidine-induced increase in mechanical threshold is mediated via the activation of M1 receptors in the spinal cord.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 814-0180, Japan. khonda@fukuoka-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Honda
authors.forename: Kohei
authors.initials: K
authors.lastname: Koga
authors.forename: Tomoko
authors.initials: T
authors.lastname: Moriyama
authors.forename: Masako
authors.initials: M
authors.lastname: Koguchi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Takano
authors.forename: Hiro-o
authors.initials: HO
authors.lastname: Kamiya
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects*; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D011930:Reaction Time / Q000187:drug effects; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D015016:Yohimbine; D003000:Clonidine