In Silico Docking and Electrophysiological Characterization of Lacosamide Binding Sites on Collapsin Response Mediator Protein 2 (crmp-2) Identifies a Pocket Important in Modulating Sodium Channel Slow Inactivation
نویسندگان
چکیده
Yuying Wang, Joel M. Brittain, Brian W. Jarecki, Ki Duk Park, Sarah M. Wilson, Bo Wang, Rachel Hale, Samy O. Meroueh, Theodore R. Cummins, and Rajesh Khanna Running head: CRMP-2 modifies LCM’s actions on Na channels From the Departments of Pharmacology and Toxicology, Chemistry, Biochemistry and Molecular Biology and Center for Computational Biology, and Bioinformatics, and Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, and Division of Medicinal Chemistry and Natural Products, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
منابع مشابه
Voltage-gated Calcium Channels Are Not Affected by the Novel Anti-epileptic Drug Lacosamide.
The novel anti-epileptic drug lacosamide targets two proteins - voltage-gated sodium channels and collapsin response mediator protein 2 (CRMP-2) - suggesting dual modes of action for lacosamide. We recently identified the neurite outgrowth and axonal guidance protein CRMP-2 as a novel partner and regulator of the presynaptic N-type voltage-gated Ca(2+) channel (CaV2.2) [Brittain et al., J. Biol...
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Lacosamide (LCM), (SPM 927, (R)-2-acetamido-N-benzyl-3-methoxypropionamide, previously referred to as harkoseride or ADD 234037) is a member of a series of functionalized amino acids that were specifically synthesized as anticonvulsive drug candidates. LCM has demonstrated antiepileptic effectiveness in different rodent seizure models and antinociceptive potential in experimental animal models ...
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Lacosamide (LCM) is a novel agent that has been developed as an antiepileptic drug. In vitro studies suggest that LCM modulates voltage-gated sodium channels by enhancing their slow inactivation. In addition, LCM seems to interact with collapsin-response mediator protein 2 and thus may mediate neuronal plasticity. LCM has an elimination half-life of 13 hours, no relevant protein binding, and do...
متن کاملAn atypical role for collapsin response mediator protein 2 (CRMP-2) in neurotransmitter release via interaction with presynaptic voltage-gated calcium channels.
Collapsin response mediator proteins (CRMPs) specify axon/dendrite fate and axonal growth of neurons through protein-protein interactions. Their functions in presynaptic biology remain unknown. Here, we identify the presynaptic N-type Ca(2+) channel (CaV2.2) as a CRMP-2-interacting protein. CRMP-2 binds directly to CaV2.2 in two regions: the channel domain I-II intracellular loop and the distal...
متن کاملLacosamide, a newer antiepileptic.
Lacosamide (LCM) is a newer antiepileptic drug with a dual mode of action. It selectively enhances slow inactivation of voltage-gated sodium channels without affecting fast inactivation, and modulates collapsing response mediator protein 2 (CRMP-2). It has a high oral bioavailability of approximately 100%. It has shown potent and broad neuroprotective effects in vitro and in vivo animal models ...
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