ABT-594, A NOVEL CHOLINERGIC CHANNEL MODULATOR, IS EFFICACIOUS IN NERVE LIGATION AND DIABETIC NEUROPATHY MODELS OF NEUROPATHIC PAIN

A novel cholinergic channel modulator, ABT-594, was tested in two esta blished 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 neurop athy models, respectively. ABT-594 produced a significant antiallodyni c effect following both oral (0.1-1 mu mol/kg) and intraperitoneal (i. p.) (0.3 mu mol/kg) administration. Equal efficacy was observed follow ing both routes of administration. ABT-594 (0.3 mu mol/kg, i.p.) maint ained efficacy following repeated dosing (5 days; twice daily) in the Chung model, but the effect of morphine (21 mu mol/kg, i.p.) was signi ficantly reduced after repeated dosing. In the diabetic neuropathy mod el, ABT-594 (0.3 mu mol/kg, i.p.) effectively reduced mechanical hyper algesia. Morphine (21 mu mol/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. ( C) 1998 Elsevier Science B.V. All rights reserved.