Pharmacopsychiatry 2003; 36 - 47
DOI: 10.1055/s-2003-825298

α-thujone reduces 5-HT3 receptor activity by an effect on the agonist-induced desensitization

T Deiml 1, R Haseneder 3, W Zieglgänsberger 2, TC Baghai 1, D Eser 1, C Schüle 1, R Ella 1, B Eisensamer 2, R Rupprecht 1, G Hapfelmeier 3
  • 1Department of Psychiatry, Klinikum Innenstadt, Ludwig-Maximilians-Universität, Munich, Germany
  • 2Department of Clinical Pharmacology, Max-Planck-Institute of Psychiatry, Munich, Germany
  • 3Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität, Munich, Germany

The convulsant effects of α-thujone, the psychotropic component of absinthe, have been attributed to inhibitory actions at the GABAA receptor. Here, we investigated for the first time the effect of α-thujone on the 5-HT3 receptor as a potential site for psychotropic actions. Our patch-clamp experiments revealed an inhibitory effect of α-thujone on both homomeric and heteromeric 5-HT3 receptors. This inhibitory action is mediated via channel blockade, even though α-thujone itself is not the channel blocking agent. In the homomeric receptors, α-thujone enhances the inherent channel blocking potency of the natural ligand 5-HT. In the heteromeric receptors, α-thujone recruits an additional channel blocking component of the agonist. Taken together, α-thujone reduces 5-HT3 receptor activity by affecting the agonist-dependent mechanisms of receptor desensitization. It remains to be shown if this inhibitory action on serotonergic responses contributes to behavioural effects of α-thujone.