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Kesingland AC, Gentry CT, Panesar MS, Bowes MA, Vernier JM, Cube R, Walker K, Urban L. 
“Analgesic profile of the nicotinic acetylcholine receptor agonists, +-epibatidine and ABT-594 in models of persistent inflammatory and neuropathic pain”. 
Pain. 2000 May 30;86(1-2):113-8.
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  • Kesingland AC
  • Gentry CT
  • Panesar MS
  • Bowes MA
  • Vernier JM
  • Cube R
  • Walker K
  • Urban L
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  • Erowid RefID: 7914
  • PubMedID: 10779668
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    Abstract
    The anti-nociceptive and locomotor effects of the nicotinic acetylcholine receptor nAChR agonists +-epibatidine and ABT-594 were compared in the rat. Acute thermal nociception was measured using the tail flick test. Mechanical hyperalgesia was measured as paw withdrawal threshold PWT in response to a mechanical stimulus in two animal models of persistent pain 1 24 h following subplantar injections of Freund's complete adjuvant FCA into the left hind paw or 2 11-15 days following a partial ligation of the left sciatic nerve. Disruption of locomotor function was assessed using an accelerating rotarod device. In all tests, +-epibatidine was significantly more potent than ABT-594. Both +-epibatidine and ABT-594 dose-dependently increased tail flick latencies but only at doses that also disrupted performance in the rotarod test. On the other hand, +-epibatidine and ABT-594 dose-dependently reversed inflammatory and neuropathic hyperalgesia at significantly lower doses than that needed to disrupt performance in the rotarod test. In summary, ABT-594 is less potent than +-epibatidine in assays of acute and persistent pain and in the rotarod assay. However, ABT-594 displayed a clearer separation between its motor and anti-hyperalgesic effects. This shows that nicotinic agonists with improved selectivity between the nicotinic receptor subtypes could provide strong analgesic effects with a much improved therapeutic window.
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