title: Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice.
abstract: Tricyclic antidepressants have analgesic and sedative effects in addition to their antidepressive properties. We tested the acute analgesic and locomotor inhibitory effects of the tricyclic antidepressant amitriptyline and the alpha(2)-adrenoceptor agonist clonidine in wild-type control and in alpha(2A)-adrenoceptor knockout mice in hot-plate and tail-flick tests. Amitriptyline-induced analgesia was lost in alpha(2A)-adrenoceptor knockout mice. The locomotor inhibitory effect of amitriptyline was reduced, but not fully abolished in alpha(2A)-adrenoceptor knockout mice. Similar results were obtained with clonidine. We conclude that alpha(2A)-adrenoceptors appear to have a significant role in amitriptyline-induced acute analgesia in mice, and that alpha(2A)-adrenoceptors also participate in the sedative effects of amitriptyline.
authors.affiliation: MediCity Research Laboratory, Department of Pharmacology and Clinical Pharmacology, University of Turku, Tykistokatu 6A, FIN-20520 Turku, Finland.
authors.forename: Umit Kazim
authors.initials: UK
authors.lastname: Ozdoğan
authors.forename: Janne
authors.initials: J
authors.lastname: Lähdesmäki
authors.forename: Heikki
authors.initials: H
authors.lastname: Mansikka
authors.forename: Mika
authors.initials: M
authors.lastname: Scheinin
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D018341:Receptors, Adrenergic, alpha-2 / Q000172:deficiency* / Q000235:genetics
chemical_list: D018712:Analgesics, Non-Narcotic; D018341:Receptors, Adrenergic, alpha-2; D000639:Amitriptyline