• James J Lynch, Carrie L Wade, Joseph P Mikusa, Michael W Decker, and Prisca Honore.
• Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Department R4N5, Bldg. AP9A-LL, 100 Abbott Park Road, Abbott Park, IL 60064-6115, USA. james.j.lynch@abbott.com
• Eur. J. Pharmacol. 2005 Feb 10; 509 (1): 43-8.

AbstractABT-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.

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