ABT-594 (a nicotinic acetylcholine agonist): Anti-allodynia in a rat chemotherapy-induced pain model

James J. Lynch, Carrie L. Wade, Joseph P. Mikusa, Michael W. Decker, Prisca Honore

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

ABT-594 ((R)-5-(2-azetidinylmethoxy)-2-chloropyridine) represents a novel class of broad-spectrum analgesics whose primary mechanism of action is activation of the neuronal nicotinic acetylcholine receptors. The present study characterized the effects of ABT-594 in a rat chemotherapy-induced neuropathic pain model, where it attenuated mechanical allodynia with an ED50=40 nmol/kg (i.p.). This anti-allodynic effect was not blocked by systemic (i.p.) pretreatment with naloxone but was blocked completely with mecamylamine. Pretreatment with chlorisondamine (0.2-5 μmol/kg, i.p.) only partially blocked the effects of ABT-594 at the higher doses tested. In contrast, central (i.c.v.) pretreatment with chlorisondamine completely blocked ABT-594's anti-allodynic effect. Taken together, the data demonstrate that ABT-594 has a potent anti-allodynic effect in the rat vincristine model and that, in addition to its strong central site of action, ABT-594's effects are partially mediated by peripheral nicotinic acetylcholine receptors in this animal model of chemotherapy-induced neuropathic pain.

Original languageEnglish (US)
Pages (from-to)43-48
Number of pages6
JournalEuropean Journal of Pharmacology
Volume509
Issue number1
DOIs
StatePublished - Feb 10 2005

Keywords

  • Allodynia
  • Analgesia
  • Cancer pain
  • Neuropathic pain
  • Nicotinic acetylcholine receptor
  • Vincristine

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