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

ABSTRACT

The anticonvulsive drug Lamotrigine (LTG) is found to activate adult muscle nicotinic acetylcholine receptors (AChR). Single-channel patch-clamp recordings showed that LTG (0.05-400 microM) applied alone is able to open AChR channels. [125I]alpha-bungarotoxin-binding studies further indicate that LTG does not bind to the canonical ACh-binding sites. 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 excess alpha-bungarotoxin, that is, when the agonist site is blocked. Allosterically-potentiating ligands or the open-channel blocker QX-314 exhibited a behavior different from that of LTG. We conclude that LTG activates the AChR through a site that is different from those of full agonists/competitive antagonists and allosterically-potentiating ligands, respectively.