Sandbox Reserved 695: Difference between revisions
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Interestingly enough, several antiepileptic drugs that are known to work by altering VGSC activity have rather distinctive structures. Phenytoin, carbamazepine, and lamotrigine have rather different structures in three-dimensional space[http://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=2981395_zmo0101062060001.jpg](click the link for an excellent illustration). These drugs all act to inhibit the VGSC to prevent high frequency depolarizations consistent with seizures. Even more interesting, these three drugs all appear to bind at the same few residues in order to exert their inhibitory effect<ref>Kuo CC. (1998) A common anticonvulsant binding site for phenytoin, carbamazepine, and lamotrigine in neuronal Na+ channels. Mol Pharmacol 54:712–721.</ref>. Bizarrely enough, this binding site also appears to overlap with the of some tricyclic antidepressants and anesthetics, although these drugs have drastically different effects from the anti-epileptic drugs.<ref>Yang, Y. C., Huang, C. S., & Kuo, C. C. (2010). Lidocaine, carbamazepine, and imipramine have partially overlapping binding sites and additive inhibitory effect on neuronal Na+ channels. Anesthesiology, 113(1), 160-174.</ref> | Interestingly enough, several antiepileptic drugs that are known to work by altering VGSC activity have rather distinctive structures. Phenytoin, carbamazepine, and lamotrigine have rather different structures in three-dimensional space[http://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=2981395_zmo0101062060001.jpg](click the link for an excellent illustration). These drugs all act to inhibit the VGSC to prevent high frequency depolarizations consistent with seizures. Even more interesting, these three drugs all appear to bind at the same few residues in order to exert their inhibitory effect<ref>Kuo CC. (1998) A common anticonvulsant binding site for phenytoin, carbamazepine, and lamotrigine in neuronal Na+ channels. Mol Pharmacol 54:712–721.</ref>. Bizarrely enough, this binding site also appears to overlap with the of some tricyclic antidepressants and anesthetics, although these drugs have drastically different effects from the anti-epileptic drugs.<ref>Yang, Y. C., Huang, C. S., & Kuo, C. C. (2010). Lidocaine, carbamazepine, and imipramine have partially overlapping binding sites and additive inhibitory effect on neuronal Na+ channels. Anesthesiology, 113(1), 160-174.</ref> | ||
The critical <scene name='Sandbox_Reserved_695/Vgsc_ligand_residues/2'>ligand binding residues</scene> for these drugs appear to be <font color='yellow'>Tyr-1771</font> and <font color='yellow'>Phe-1764</font>.<ref>Ragsdale DS, Avoli M. (1998) Sodium channels as molecular targets for antiepileptic drugs. Brain Res Rev 26:16–28</ref> | |||
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