Abstract
This research was designed to determine the action of the novel aminoalkylindole AM630 (6-iodo-pravadoline) at the cannabinoid receptor by studying its interaction with the cannabinoid receptor agonist WIN 55,212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]-1,4-benzoxazin-y]-(1-naphthalenyl)methanone mesylate) on guanosine-5'-O-(3-[35S]thio) triphosphate ([35S]GTP gamma S) binding in mouse brain. WIN 55,212-2 stimulated [35S]GTP gamma S binding, while AM630 had no effect. AM630 antagonized WIN 55,212-2-2induced [35S]GTP gamma S binding and shifted the WIN 55,212-dose-response curve to the right. These results clearly demonstrate that AM630 exerts cannabinoid receptor antagonist properties in the brain.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesics / pharmacology
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Animals
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Benzoxazines
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Brain / drug effects*
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Brain / metabolism
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Cannabinoids / antagonists & inhibitors*
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Cannabinoids / pharmacology
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism*
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Indoles / pharmacology*
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Male
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Membranes / drug effects
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Membranes / metabolism
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Mice
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Mice, Inbred ICR
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Morpholines / pharmacology
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Naphthalenes / pharmacology
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Receptors, Cannabinoid
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Receptors, Drug / agonists
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Receptors, Drug / antagonists & inhibitors
Substances
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Analgesics
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Benzoxazines
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Cannabinoids
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Indoles
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Morpholines
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Naphthalenes
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Receptors, Cannabinoid
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Receptors, Drug
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Guanosine 5'-O-(3-Thiotriphosphate)
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(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
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iodopravadoline