EFFECTS OF LAMOTRIGINE ON THE 5-MT1A RECEPTOR FUNCTION IN HEALTHY-HUMAN MALES

Background: Lamotrigine, a new anticonvulsant, has recently been repor ted to be effective in treating patients with bipolar mania, depressio n, and schizoaffective disorder, suggesting that it is perhaps a mood stabilizer with antimanic and antidepressant properties. However, the mechanism of action underlying its efficacy in mood disorders is still unknown. Methods: To explore the role of 5-HT1A receptors in the mech anism of action of lamotrigine, we measured the body temperature and p lasma cortisol responses to a challenge with a selective 5-HT1A recept or agonist ipsapirone in ten healthy human males. Each subject receive d 0.3 mg/kg of ipsapirone hydrochloride tablets at time ''0''. Body te mperature readings and blood samples for cortisol levels were obtained at 0, 30, 60, 90, 120, 150, 180 min. The ipsapirone challenge tests w ere repeated after 1 week treatment with lamotrigine (100 mg/day). Res ults: Treatment with lamotrigine for 1 week did not significantly alte r the hypothermic or cortisol responses to ipsapirone. Limitations: Th e limitations of this study included small sample size, low treatment dose, short treatment interval, and lack of placebo control. Conclusio ns: Our findings might suggest that 5-HT1A receptor function is not-in volved in the mechanism of action of lamotrigine in humans. Further pl acebo-controlled studies with a higher lamotrigine dose and a longer t reatment interval in a larger number of subjects are needed to verify this. (C) 1998 Elsevier Science B.V.