AM630 antagonism of cannabinoid-stimulated [35S]GTP gamma S binding in the mouse brain

Eur J Pharmacol. 1997 Feb 19;321(1):R1-3. doi: 10.1016/s0014-2999(97)00047-2.

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

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

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Benzoxazines
  • Brain / drug effects*
  • Brain / metabolism
  • Cannabinoids / antagonists & inhibitors*
  • Cannabinoids / pharmacology
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism*
  • Indoles / pharmacology*
  • Male
  • Membranes / drug effects
  • Membranes / metabolism
  • Mice
  • Mice, Inbred ICR
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists
  • Receptors, Drug / antagonists & inhibitors

Substances

  • Analgesics
  • Benzoxazines
  • Cannabinoids
  • Indoles
  • Morpholines
  • Naphthalenes
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • iodopravadoline