Synthesis and biological evaluation of a fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain and imaging agent |
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Authors: | Thomas H Walls Scott C Grindrod Dawn Beraud Li Zhang Aparna R Baheti Sivanesan Dakshanamurthy Manoj K Patel Milton L Brown Linda H Macarthur |
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Institution: | Drug Discovery Program, Department of Oncology, Georgetown University Medical Center, 3970 Reservoir Rd., NW, Washington, DC 20057, USA. |
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Abstract: | Here we report on a novel fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain with potential use as an imaging agent. Compound 2 incorporated a heptyl side chain and dansyl moiety onto the parent compound phenytoin and produced greater displacement of BTX from sodium channels and greater functional blockade with greatly reduced toxicity. Compound 2 reduced mechano-allodynia in a rat model of neuropathic pain and was visualized ex vivo in sensory neuron axons with two-photon microscopy. These results suggest a promising strategy for developing novel sodium channel inhibitors with imaging capabilities. |
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