Open AccessDrug Binding Assays do not Reveal Specific Binding of Lacosamide to Collapsin Response Mediator Protein 2 (CRMP‐2)
Author(s) -
Wolff Christian,
Carrington Bruce,
VarrinDoyer Michel,
Vandendriessche Anne,
Van der Perren Christy,
Famelart Michel,
Gillard Michel,
Foerch Patrik,
Rogemond Véronique,
Honnorat Jerôme,
Lawson Alastair,
Miller Karen
Publication year - 2012
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/j.1755-5949.2012.00313.x
Subject(s) - lacosamide , mediator , drug , pharmacology , chemistry , neuroscience , medicine , biology , epilepsy
SUMMARY Aims: 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. Conclusion: 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.