The antiepileptic drug Lamotrigine has a dual agonist- channel blocker activity on the nicotinic acetylcholine receptor.

VALLES, A. S.; GARBUS, I.; ANTOLLINI, S. S.; BARRANTES, F. J.

Toronto, Canada

Congreso; First annual meeting of the Canadian Association for Neuroscience; 2007

Lamotrigine (LTG) is an antiepileptic drug employed in the treatment  of partial epilepsies. We studied its possible interaction with  channels other than its known therapeutic target, the voltage gated  sodium channel, using the adult muscle nicotinic acetylcholine  receptor (AChR) as a model. Patch-clamp recordings showed that LTG  (50-400 ?M) affected AChR channel function, behaving as an  open-channel blocker when co-applied with the natural agonist,  acetylcholine (Vallés et al., NeuroReport. 18(1):45-50, January 8,  2007). Here, single-channel recordings with LTG alone demonstrate that  LTG (0.05-100 ?M) is able to activate the AChR channel by itself.  [125I]-?-bungarotoxin binding studies further indicate that LTG does  not bind to the ACh binding site. Moreover, fluorescence experiments  using the probe crystal violet, which displays higher affinity for the  desensitized (D, in the presence of agonist) than for the resting AChR  conformation (R, in the absence of agonist) show that LTG is able to  induce the transition from the R-state to the D-state in the presence  of a-bungarotoxin, i.e. when the canonical agonist binding site is  blocked. We conclude that LTG displays dual agonist /channel blocker  activities on the AChR, operating through different sites.