Relative efficacies of cannabinoid CB1 receptor agonists in the mouse brain

Eur J Pharmacol. 1997 Oct 8;336(2-3):295-8. doi: 10.1016/s0014-2999(97)01255-7.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonic Acids / metabolism
  • Arachidonic Acids / pharmacology
  • Brain / metabolism*
  • Cannabinoids / metabolism*
  • Cannabinoids / pharmacology*
  • Cells, Cultured
  • Cyclohexanols / metabolism
  • Cyclohexanols / pharmacology
  • Dronabinol / analogs & derivatives
  • Dronabinol / metabolism
  • Dronabinol / pharmacology
  • Endocannabinoids
  • Enzyme Activation
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Piperidines / metabolism
  • Polyunsaturated Alkamides
  • Pyrazoles / metabolism
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists*
  • Receptors, Drug / metabolism
  • Rimonabant

Substances

  • Arachidonic Acids
  • Cannabinoids
  • Cyclohexanols
  • Endocannabinoids
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Dronabinol
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • GTP-Binding Proteins
  • HU 211
  • Rimonabant
  • anandamide