A novel agonist effect on the nicotinic acetylcholine receptor is exerted by the anticonvulsive drug Lamotrigine

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

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Elsevier

Año: 2008 vol. 1778 p. 2395 - 2404

0005-2736

The anticonvulsive drug Lamotrigine (LTG) is found to activate adult muscle nicotinic acetylcholine receptors (AChR). Single-channel patch-clamp recordings showed that the application of LTG (0.05-100 ìM) alone is able to open AChR channels by itself. [125I]a-bungarotoxin binding studies further indicate that LTG does not bind to the canonical ACh binding site. Moreover, fluorescence experiments using the probe crystal violet demonstrate that LTG induces the transition from the resting state to the desensitized state of the AChR in the presence of a-bungarotoxin, that is, when the agonist site is blocked. Allosterically-potentiating ligands or an open-channel blocker exhibited a behavior different from that of LTG. We conclude that LTG activates the AChR through a site that is different from that of the agonist/competitive antagonists and that of allosterically-potentiating ligands.