title: ABT-594, a novel cholinergic channel modulator, is efficacious in nerve ligation and diabetic neuropathy models of neuropathic pain.
abstract: A novel cholinergic channel modulator, ABT-594, was tested in two established and distinct models of neuropathic pain; the Chung model (i.e., tight ligation of L5 and L6 spinal nerves) and a diabetic neuropathy model (i.e., streptozotocin-induced diabetes). Tactile allodynia and mechanical hyperalgesia were assessed in the Chung and diabetic neuropathy models, respectively. ABT-594 produced a significant antiallodynic effect following both oral (0.1-1 micromol/kg) and intraperitoneal (i.p.) (0.3 micromol/kg) administration. Equal efficacy was observed following both routes of administration. ABT-594 (0.3 micromol/kg, i.p.) maintained efficacy following repeated dosing (5 days; twice daily) in the Chung model, but the effect of morphine (21 micromol/kg, i.p.) was significantly reduced after repeated dosing. In the diabetic neuropathy model, ABT-594 (0.3 micromol/kg, i.p.) effectively reduced mechanical hyperalgesia. Morphine (21 micromol/kg, i.p.) was not effective in this model. Overall, these results suggest development of ABT-594 may provide a novel pharmacotherapy for the chronic treatment of neuropathic pain.
authors.affiliation: Neurological and Urological Diseases Research, D-47W, Pharmaceutical Products Division, Abbott Laboratories, 100 Abbott Park Road, Bldg., AP-9A LL, Abbott Park, IL 60064-3500, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Bannon
authors.forename: M W
authors.initials: MW
authors.lastname: Decker
authors.forename: D J
authors.initials: DJ
authors.lastname: Kim
authors.forename: J E
authors.initials: JE
authors.lastname: Campbell
authors.forename: S P
authors.initials: SP
authors.lastname: Arneric
mesh_terms: D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic; D000818:Animals; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy; D007274:Injections, Intraperitoneal; D008026:Ligation; D008161:Lumbosacral Region; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects* / Q000502:physiology*; D013997:Time Factors
chemical_list: C109763:5-(2-azetidinylmethoxy)-2-chloropyridine; D018712:Analgesics, Non-Narcotic; D001384:Azetidines; D018680:Cholinergic Antagonists; D011725:Pyridines; D009020:Morphine