title: Synthesis and biological evaluation of a fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain and imaging agent.
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.
authors.affiliation: Drug Discovery Program, Department of Oncology, Georgetown University Medical Center, 3970 Reservoir Rd., NW, Washington, DC 20057, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Walls
authors.forename: Scott C
authors.initials: SC
authors.lastname: Grindrod
authors.forename: Dawn
authors.initials: D
authors.lastname: Beraud
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Aparna R
authors.initials: AR
authors.lastname: Baheti
authors.forename: Sivanesan
authors.initials: S
authors.lastname: Dakshanamurthy
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Patel
authors.forename: Milton L
authors.initials: ML
authors.lastname: Brown
authors.forename: Linda H
authors.initials: LH
authors.lastname: MacArthur
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015195:Drug Design; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009437:Neuralgia / Q000188:drug therapy*; D010672:Phenytoin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D005456:Fluorescent Dyes; D026941:Sodium Channel Blockers; D010672:Phenytoin