SR141716A is an inverse agonist at the human cannabinoid CB1 receptor

Eur J Pharmacol. 1997 Sep 3;334(1):R1-2. doi: 10.1016/s0014-2999(97)01160-6.

Abstract

The effects of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4- benzoxazin-yl]-(1-napthalenyl)methanone mesylate (WIN 55,212-2) and N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazo le-carboxamide (SR141716A) on guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding to membranes isolated from human cannabinoid CB1 receptor-transfected Chinese hamster ovary (CHO) cells were examined. WIN 55,212-2 stimulated [35S]GTPgammaS binding 76.3% above basal levels whereas SR141716A produced a 22.3% decrease in basal [35S]GTPgammaS binding. These findings demonstrate that WIN 55,212-2 is an agonist and SR141716A is an inverse agonist in this system.

Publication types

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

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Benzoxazines
  • Binding, Competitive
  • CHO Cells / drug effects
  • Cricetinae
  • Humans
  • Morpholines / pharmacology*
  • Naphthalenes / pharmacology*
  • Piperidines / pharmacology*
  • Pyrazoles / pharmacology*
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists*
  • Receptors, Drug / drug effects
  • Receptors, Drug / metabolism
  • Rimonabant
  • Transfection

Substances

  • Analgesics
  • Benzoxazines
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Rimonabant