Abstract
In the present work, we have designed and synthesized a series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter (IC(50) = 24-0.8 microM, K(i) > 1000-5000 nM for CB(1) and CB(2) cannabinoid receptors and vanilloid VR(1) receptor). Among them, N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide deserves special attention as being the most potent endocannabinoid transporter inhibitor (IC(50) = 0.8 microM) described to date.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arachidonic Acids / chemical synthesis*
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Arachidonic Acids / chemistry
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Arachidonic Acids / metabolism
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Arachidonic Acids / pharmacology
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Cannabinoid Receptor Modulators
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Cannabinoids / metabolism*
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Carrier Proteins / antagonists & inhibitors*
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Carrier Proteins / metabolism
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Cell Line
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Cerebellum / metabolism
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Drug Design
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Endocannabinoids
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Furans / chemical synthesis*
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Furans / chemistry
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Furans / pharmacology
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Humans
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In Vitro Techniques
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Membranes
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Polyunsaturated Alkamides
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Radioligand Assay
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Receptors, Cannabinoid
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Receptors, Drug / metabolism
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Spinal Cord / metabolism
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Structure-Activity Relationship
Substances
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Arachidonic Acids
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Cannabinoid Receptor Modulators
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Cannabinoids
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Carrier Proteins
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Endocannabinoids
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Furans
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N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide
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Polyunsaturated Alkamides
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Receptors, Cannabinoid
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Receptors, Drug
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anandamide