Drug binding assays do not reveal specific binding of lacosamide to collapsin response mediator protein 2 (CRMP-2).
OBJECTIVE
Lacosamide (LCM; SPM 927, Vimpat®) is an antiepileptic drug (AED) used as adjunctive treatment for adults with partial-onset seizures. LCM has a different mode of action from traditional sodium channel blocking AEDs in that it selectively enhances slow inactivation of sodium channels without affecting fast inactivation. Initial investigations suggested that LCM might have an additional mode of action by binding to the collapsin response mediator protein 2 (CRMP-2), which is further investigated here.


METHODS
LCM binding to native and cloned human CRMP-2 was determined using radioligand binding experiments and surface plasmon resonance measurements.


RESULTS
No specific binding of [(3) H]LCM (free concentration 100-1450 nM) to isolated or membrane bound human CRMP-2 expressed in mammalian cell systems and bacteria was observed. Surface plasmon resonance analysis also showed that LCM, over a concentration range of 0.39-100 μM, does not specifically bind to human CRMP-2.


CONCLUSIONS
The diverse drug binding methods employed here are well suited to detect specific binding of LCM to CRMP-2 in the micromolar range, yet the results obtained were all negative. Results of this study suggest that LCM does not specifically bind to CRMP-2.
UCB Pharma, CNS Research, Braine l'Alleud, Belgium. Christian.Wolff@ucb.com
Christian
C
Wolff
Bruce
B
Carrington
Michel
M
Varrin-Doyer
Anne
A
Vandendriessche
Christy
C
Van der Perren
Michel
M
Famelart
Michel
M
Gillard
Patrik
P
Foerch
Véronique
V
Rogemond
Jerôme
J
Honnorat
Alastair
A
Lawson
Karen
K
Miller
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000078334:Lacosamide; D008297:Male; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009865:Oocytes; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D020349:Surface Plasmon Resonance; D014162:Transfection; D014316:Tritium / Q000493:pharmacokinetics; D014981:Xenopus
D000081:Acetamides; D000927:Anticonvulsants; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2; D014316:Tritium; D000078334:Lacosamide