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: A W Bannon, M W Decker, D J Kim, J E Campbell, S P Arneric
• Journal: Brain research (Brain Res) Vol. 801 Issue 1-2 Pg. 158-63 (Aug 10 1998) ISSN: 0006-8993 [Print] Netherlands
• PMID: 9729357 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright 1998 Elsevier Science B.V.

Chemical References

• 5-(2-azetidinylmethoxy)-2-chloropyridine
• Analgesics, Non-Narcotic
• Azetidines
• Cholinergic Antagonists
• Pyridines
• Morphine

Topics

• Administration, Oral
• Analgesics, Non-Narcotic
• Animals
• Azetidines (administration & dosage, pharmacology)
• Cholinergic Antagonists (metabolism)
• Diabetes Mellitus, Experimental
• Diabetic Neuropathies (drug therapy)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Hyperalgesia (drug therapy)
• Injections, Intraperitoneal
• Ligation
• Lumbosacral Region
• Male
• Morphine (administration & dosage, pharmacology)
• Pain (drug therapy)
• Pyridines (administration & dosage, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Spinal Nerves (drug effects, physiology)
• Time Factors