Effects of lamotrigine on the 5-HT1A receptor function in healthy human males.
BACKGROUND
Lamotrigine, a new anticonvulsant, has recently been reported to be effective in treating patients with bipolar mania, depression, 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 mechanism of action of lamotrigine, we measured the body temperature and plasma cortisol responses to a challenge with a selective 5-HT1A receptor agonist ipsapirone in ten healthy human males. Each subject received 0.3 mg/kg of ipsapirone hydrochloride tablets at time "0". Body temperature readings and blood samples for cortisol levels were obtained at 0, 30, 60, 90, 120, 150, 180 min. The ipsapirone challenge tests were repeated after 1 week treatment with lamotrigine (100 mg/day).


RESULTS
Treatment with lamotrigine for 1 week did not significantly alter the hypothermic or cortisol responses to ipsapirone.


CONCLUSIONS
The limitations of this study included small sample size, low treatment dose, short treatment interval, and lack of placebo control.


CONCLUSIONS
Our findings might suggest that 5-HT1A receptor function is not involved in the mechanism of action of lamotrigine in humans. Further placebo-controlled studies with a higher lamotrigine dose and a longer treatment interval in a larger number of subjects are needed to verify this.
Shiah
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Department of Psychiatry, the University of British Columbia, Vancouver, Canada.
Yatham
L N
LN
Lam
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Zis
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AP
D000328:Adult; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced; D000077213:Lamotrigine; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology*
D000927:Anticonvulsants; D011743:Pyrimidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014227:Triazines; C043077:ipsapirone; D000077213:Lamotrigine; D006854:Hydrocortisone