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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.


Umit Kazim Ozdoğan, Janne Lähdesmäki, Heikki Mansikka, Mika Scheinin. Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice. European journal of pharmacology. 2004 Feb 6;485(1-3):193-6

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PMID: 14757140

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