Abstract
We measured (-)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohe xyl]-phenol (CP 55,940)-, (-)11-OH-delta8-tetrahydrocannabinol-dimethylheptyl (HU-210)-, anandamide- and delta9-tetrahydrocannabinol-stimulated G protein activation in mouse brain using the [35S]GTPgammaS functional assay. The Ki values for these drugs were determined by agonist competition binding with the cannabinoid CB1 receptor antagonist [3H]N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carboxamidehydrochloride ([3H]SR141716A). This information was used to calculate the efficacy for drug stimulation of G protein activity. The rank order of efficacy was CP 55,940 > HU-210 > anandamide > delta9-tetrahydrocannabinol with the latter two drugs being partial agonists. Since efficacy values relate receptor occupancy to functional responses, we believe efficacy values are a better measure of drug-mediated functional responses compared with measurements of drug potency.
Publication types
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Comparative Study
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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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Animals
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Arachidonic Acids / metabolism
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Arachidonic Acids / pharmacology
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Brain / metabolism*
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Cannabinoids / metabolism*
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Cannabinoids / pharmacology*
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Cells, Cultured
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Cyclohexanols / metabolism
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Cyclohexanols / pharmacology
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Dronabinol / analogs & derivatives
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Dronabinol / metabolism
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Dronabinol / pharmacology
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Endocannabinoids
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Enzyme Activation
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GTP-Binding Proteins / metabolism*
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
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Male
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Mice
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Mice, Inbred ICR
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Piperidines / metabolism
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Polyunsaturated Alkamides
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Pyrazoles / metabolism
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Receptors, Cannabinoid
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Receptors, Drug / agonists*
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Receptors, Drug / metabolism
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Rimonabant
Substances
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Arachidonic Acids
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Cannabinoids
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Cyclohexanols
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Endocannabinoids
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Piperidines
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Polyunsaturated Alkamides
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Pyrazoles
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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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Dronabinol
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3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
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GTP-Binding Proteins
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HU 211
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Rimonabant
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anandamide