Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice.
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.
Ozdoğan
Umit Kazim
UK
MediCity Research Laboratory, Department of Pharmacology and Clinical Pharmacology, University of Turku, Tykistokatu 6A, FIN-20520 Turku, Finland.
Lähdesmäki
Janne
J
Mansikka
Heikki
H
Scheinin
Mika
M
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
D018712:Analgesics, Non-Narcotic; D018341:Receptors, Adrenergic, alpha-2; D000639:Amitriptyline