Abstract
Paradoxically, some TRPV1 agonists are, at the organismal level, both nonpungent and clinically useful as topical analgesics. Here, we describe the scaled-up synthesis and characterization in mouse models of a novel, nonpungent vanilloid. Potent analgesic activity was observed in models of neuropathic pain, and the compound blocked capsaicin induced allodynia, showing dermal accumulation with little transdermal absorption. Finally, it displayed much weaker systemic toxicity compared to capsaicin and was negative in assays of genotoxicity.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics / chemical synthesis
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Analgesics / pharmacokinetics
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Analgesics / therapeutic use*
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Analgesics / toxicity
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Animals
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CHO Cells
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Capsaicin
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Cricetulus
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Drug Discovery
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Hyperalgesia / chemically induced
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Hyperalgesia / drug therapy
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Mice, Inbred ICR
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Neuralgia / drug therapy
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Phenylurea Compounds / chemical synthesis
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Phenylurea Compounds / pharmacokinetics
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Phenylurea Compounds / therapeutic use*
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Phenylurea Compounds / toxicity
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Swine
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TRPV Cation Channels / agonists*
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Thiazoles / chemical synthesis
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Thiazoles / pharmacokinetics
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Thiazoles / therapeutic use*
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Thiazoles / toxicity
Substances
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Analgesics
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Phenylurea Compounds
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TRPV Cation Channels
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TRPV1 receptor
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Thiazoles
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Capsaicin