title: Neuroprotective effects of Kv7 channel agonist, retigabine, for cisplatin-induced peripheral neuropathy.
abstract: Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of many commonly used chemotherapeutic agents. One mechanism underlying this neuronal damage is via drug-induced membrane depolarization. Accordingly, one potential approach for preventing chemotherapy-induced neuropathy is via the forced maintenance of normal membrane potential during exposure to the toxic drug. More specifically, intentional elevation of the slow K(+) current, via activation of Kv7 channels with a resultant hyperpolarizing shift, could be theoretically neuroprotective. In this study, in vivo nerve excitability testing in sensory nerves in mice was used to evaluate the potential therapeutic role of retigabine, a Kv7 channel activator, in the prevention of cisplatin-induced neurodegeneration. It was found that cisplatin caused membrane depolarization and peripheral axon loss that were partially prevented by retigabine pretreatment. These results support the general concept that chemotherapy-induced neuropathy can be partially inhibited via Kv7 channel activation.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA. hodera@bidmc.harvard.edu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nodera
authors.forename: Andrew
authors.initials: A
authors.lastname: Spieker
authors.forename: Minhee
authors.initials: M
authors.lastname: Sung
authors.forename: Seward
authors.initials: S
authors.lastname: Rutkove
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002219:Carbamates / Q000627:therapeutic use*; D002945:Cisplatin / Q000633:toxicity*; D004195:Disease Models, Animal; D004347:Drug Interactions; D007274:Injections, Intraperitoneal / Q000379:methods; D008297:Male; D051379:Mice; D009431:Neural Conduction / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D010655:Phenylenediamines / Q000627:therapeutic use*; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D002219:Carbamates; D018696:Neuroprotective Agents; D010655:Phenylenediamines; D026902:Potassium Channel Blockers; C101866:ezogabine; D002945:Cisplatin