Source:http://linkedlifedata.com/resource/pubmed/id/20562022
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2010-7-8
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| pubmed:abstractText |
The treatment of chronic pain is hampered by various issues including multiple underlying mechanisms contributing to disease pathology and treatment-related toxicity concerns. These can be partially circumvented by combining mechanistically distinct drugs with the aim of selectively potentiating analgesia as opposed to side-effects. This approach has been used to assess the antinociceptive efficacy of the nicotinic acetylcholine (nACh) receptor agonist ABT-594 when combined with the antiepileptic drug gabapentin, the mu-opioid receptor agonist morphine or the antidepressant drug duloxetine in the rat formalin test. Alone, ABT-594 (0.01-0.3 mg/kg) dose-dependently attenuated spontaneous flinching behaviour during first (P1) and second (P2) phase. Similarly, P1, interphase and P2 flinching were variously attenuated by gabapentin (25-200 mg/kg), morphine (0.3-3 mg/kg) and duloxetine (3-60 mg/kg). Remarkably, a completely inactive dose of ABT-594 reduced the dose of gabapentin required to produce antinociception during P1 by 4-8 fold and during P2 by 8-16 fold. This striking potentiation was blocked by mecamylamine and indicative of analgesic synergy. Similar, albeit less consistent results (3-10 fold potency increase) were obtained with morphine/ABT-594. Although a 3 fold increase in P2 antinociceptive potency was obtained with duloxetine in the presence of ABT-594, a corresponding increase in efficacy was lacking. Indeed, a mechanistically relevant reduction in antinociceptive efficacy and potency of duloxetine/ABT-594 occurred during interphase. Thus, activation of the nicotinic cholinergic system differentially modulates the antinociceptive actions of distinct mechanism of action compounds, and provides a novel framework for nACh receptor modulators mediating analgesia in the putative absence of adverse events associated with this mechanism of action.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-(2-azetidinylmethoxy)-2-chloropyri...,
http://linkedlifedata.com/resource/pubmed/chemical/Amines,
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics,
http://linkedlifedata.com/resource/pubmed/chemical/Azetidines,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclohexanecarboxylic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Mecamylamine,
http://linkedlifedata.com/resource/pubmed/chemical/Morphine,
http://linkedlifedata.com/resource/pubmed/chemical/Nicotinic Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Nicotinic Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Thiophenes,
http://linkedlifedata.com/resource/pubmed/chemical/duloxetine,
http://linkedlifedata.com/resource/pubmed/chemical/gabapentin,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Aminobutyric Acid
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1873-7064
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2010 Elsevier Ltd. All rights reserved.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
59
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
208-17
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| pubmed:meshHeading |
pubmed-meshheading:20562022-Amines,
pubmed-meshheading:20562022-Analgesics,
pubmed-meshheading:20562022-Animals,
pubmed-meshheading:20562022-Azetidines,
pubmed-meshheading:20562022-Cyclohexanecarboxylic Acids,
pubmed-meshheading:20562022-Disease Models, Animal,
pubmed-meshheading:20562022-Dose-Response Relationship, Drug,
pubmed-meshheading:20562022-Drug Synergism,
pubmed-meshheading:20562022-Exploratory Behavior,
pubmed-meshheading:20562022-Male,
pubmed-meshheading:20562022-Mecamylamine,
pubmed-meshheading:20562022-Morphine,
pubmed-meshheading:20562022-Nicotinic Agonists,
pubmed-meshheading:20562022-Nicotinic Antagonists,
pubmed-meshheading:20562022-Pain,
pubmed-meshheading:20562022-Pain Measurement,
pubmed-meshheading:20562022-Pyridines,
pubmed-meshheading:20562022-Rats,
pubmed-meshheading:20562022-Rats, Sprague-Dawley,
pubmed-meshheading:20562022-Thiophenes,
pubmed-meshheading:20562022-gamma-Aminobutyric Acid
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| pubmed:year |
2010
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| pubmed:articleTitle |
Selective potentiation of gabapentin-mediated antinociception in the rat formalin test by the nicotinic acetylcholine receptor agonist ABT-594.
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| pubmed:affiliation |
Department of Pharmacology, NeuroSearch A/S, 93 Pederstrupvej, DK-2750, Ballerup, Denmark. gmu@neurosearch.dk
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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