title: Broad-spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors.
abstract: 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.
authors.affiliation: Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Bannon
authors.forename: M W
authors.initials: MW
authors.lastname: Decker
authors.forename: M W
authors.initials: MW
authors.lastname: Holladay
authors.forename: P
authors.initials: P
authors.lastname: Curzon
authors.forename: D
authors.initials: D
authors.lastname: Donnelly-Roberts
authors.forename: P S
authors.initials: PS
authors.lastname: Puttfarcken
authors.forename: R S
authors.initials: RS
authors.lastname: Bitner
authors.forename: A
authors.initials: A
authors.lastname: Diaz
authors.forename: A H
authors.initials: AH
authors.lastname: Dickenson
authors.forename: R D
authors.initials: RD
authors.lastname: Porsolt
authors.forename: M
authors.initials: M
authors.lastname: Williams
authors.forename: S P
authors.initials: SP
authors.lastname: Arneric
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001384:Azetidines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008024:Ligands; D008464:Mecamylamine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009469:Neuromuscular Junction / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: C109763:5-(2-azetidinylmethoxy)-2-chloropyridine; D018712:Analgesics, Non-Narcotic; D001384:Azetidines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008024:Ligands; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine; D009020:Morphine; C082748:epibatidine; D002211:Capsaicin