The antinociceptive effects of the novel phentylethylamine antidepressant drug venlafaxine and its interaction with various opioid, noradrenaline and serotonin receptor subtypes were evaluated. When mice were tested with a hotplate analgesia meter, venlafaxine induced a dose-dependent antinociceptive effect following i.p. administration with an ED50 of 46.7 mg/kg (20.5; 146.5; 95% CL). Opioid, adrenergic and serotoninergic receptor antagonists were tested for their ability to block venlafaxine antinociception. Venlafaxine-induced antinociception was significantly inhibited by naloxone, nor-BNI and naltrindole but not by β-FNA or naloxonazine, implying involvement of κ1- and δ-opioid mechanisms. When adrenergic and serotoninergic antagonists were used, yohimbine (P<0.005) but not phentolamine or metergoline, decreased antinociception elicited by venlafaxine, implying a clear α2- and a minor α1-adrenergic mechanism of antinociception. When venlafaxine was administered together with various agonists of the opioid and α2- receptor subtypes, it significantly potentiated antinociception mediated by κ1- κ3- and δ-opioid receptor subtypes. The α2-adrenergic agonist clonidine significantly potentiated venlafaxine-mediated antinociception. Summing up these results, we conclude that the antinociceptive effect of venlafaxine is mainly influenced by the κ- and δ-opioid receptor subtypes combined with the α2-adrenergic receptor. These results suggest a potential use of venlafaxine in the management of some pain syndromes. However, further research is needed in order to establish both the exact clinical indications and the effective doses of venlafaxine when prescribed for pain. Copyright (C) 1999 Elsevier Science Ireland Ltd.
|Number of pages||4|
|State||Published - 1 Oct 1999|
- Opioid receptor subtypes