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

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 micromol/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.

• Authors: James J Lynch 3rd, Carrie L Wade, Joseph P Mikusa, Michael W Decker, Prisca Honore
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 509 Issue 1 Pg. 43-8 (Feb 10 2005) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15713428 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 5-(2-azetidinylmethoxy)-2-chloropyridine
• Azetidines
• Nicotinic Agonists
• Pyridines
• Naloxone
• Vincristine
• Mecamylamine
• Chlorisondamine
• Acetylcholine

Topics

• Acetylcholine (agonists, pharmacology)
• Analgesia (methods)
• Animals
• Azetidines (antagonists & inhibitors, chemistry, pharmacology)
• Chlorisondamine (administration & dosage, pharmacokinetics)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Routes
• Drug Administration Schedule
• Drug Evaluation, Preclinical (methods)
• Drug Therapy, Combination
• Humans
• Mecamylamine (administration & dosage, pharmacokinetics)
• Naloxone (administration & dosage)
• Nicotinic Agonists (chemistry, pharmacology)
• Pain (chemically induced)
• Pyridines (antagonists & inhibitors, chemistry, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Time Factors
• Vincristine (administration & dosage, adverse effects, pharmacokinetics)