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Science 2 January 1998:
Vol. 279. no. 5347, pp. 77 - 80
DOI: 10.1126/science.279.5347.77
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Reports

Broad-Spectrum, Non-Opioid Analgesic Activity by Selective Modulation of Neuronal Nicotinic Acetylcholine Receptors

A. W. Bannon, * M. W. Decker, dagger M. W. Holladay, P. Curzon, D. Donnelly-Roberts, P. S. Puttfarcken, R. S. Bitner, A. Diaz, A. H. Dickenson, R. D. Porsolt, M. Williams, S. P. Arneric

Development of analgesic agents for the treatment of severe pain requires the identification of compounds that are devoid of opioid receptor liabilities. A potent (inhibition constant = 37 picomolar) neuronal nicotinic acetylcholine receptor (nAChR) ligand called ABT-594 was developed that has antinociceptive properties equal in efficacy to those of morphine across a series of diverse animal models of acute thermal, persistent chemical, and neuropathic pain states. These effects were blocked by the nAChR antagonist mecamylamine. In contrast to morphine, repeated treatment with ABT-594 did not appear to elicit opioid-like withdrawal or physical dependence. Thus, ABT-594 may be an analgesic that lacks the problems associated with opioid analgesia.

A. W. Bannon, M. W. Decker, M. W. Holladay, P. Curzon, D. Donnelly-Roberts, P. S. Puttfarcken, R. S. Bitner, M. Williams, S. P. Arneric, Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500. USA.
A. Diaz and A. H. Dickenson, Neuropharmacology of Pain Group, University College London, London, WC1E 6BT, UK.
R. D. Porsolt, ITEM-LABO, 94276 Le Kremlin Bicetre Cedex, France.
*   Present address: AMGEN, Inc., Thousand Oaks, CA 91320, USA.

dagger    To whom correspondence should be addressed. E-mail: michael.w.decker{at}abbott.com

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