SR141716A is an inverse agonist at the human cannabinoid CB1 receptor.

  title={SR141716A is an inverse agonist at the human cannabinoid CB1 receptor.},
  author={R. Landsman and T. Burkey and P. Consroe and W. Roeske and H. Yamamura},
  journal={European journal of pharmacology},
  volume={334 1},
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… Expand
Inhibitory effects of SR141716A on G-protein activation in rat brain.
It is demonstrated that SR141716A is a competitive antagonist at nanomolar concentrations, whereas it inhibits basal receptor-mediated G-protein activity at micromolar concentrations. Expand
Cannabinoid receptor antagonism and inverse agonism in response to SR141716A on cAMP production in human and rat brain.
A ligand-independent activity for cannabinoid CB(1) receptor signaling cascade in mammalian brain is suggested through the activation of G(i/o) proteins. Expand
Role of the endogenous cannabinoid system in the formalin test of persistent pain in the rat.
The results suggest that, in this model, endogenous cannabinoids do not tonically attenuate inflammatory hyperalgesia and cannabinoid antagonists do not enhance formalin-evoked pain behaviour. Expand
Involvement of other neurotransmitters in behaviors induced by the cannabinoid CB1 receptor antagonist SR 141716A in naive mice
Since SR 141716A lacks affinity for the discussed receptors, it appears that the induction of the cited behaviors probably involve indirect activation of their respective neurotransmitter systems. Expand
Inverse agonist properties of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR141716A) and 1-(2-chlorophenyl)-4-cyano-5-(4-methoxyphenyl)-1H-pyrazole-3-carboxyl ic acid phenylamide (CP-272871) for the CB(1) cannabinoid receptor.
It is demonstrated that the aryl pyrazoles SR141716A and CP-272871 behave as antagonists and as inverse agonists in G-protein-mediated signal transduction in preparations of endogenously expressed CB(1) receptors. Expand
Characterization of the pharmacology of imidazolidinedione derivatives at cannabinoid CB1 and CB2 receptors.
These derivatives exhibit different activities (neutral antagonism and inverse agonism) in the different models of cannabinoid receptors studied, indicating that they act as cannabinoid CB1 receptor neutral antagonists. Expand
In vitro and in vivo pharmacology of CP-945,598, a potent and selective cannabinoid CB(1) receptor antagonist for the management of obesity.
In vivo, in vitro, ex vivo, and in vivo data indicate that CP-945,598 is a novel CB(1) receptor competitive antagonist that may further the understanding of the endocannabinoid system. Expand
(2S,3R)β-Methyl-2′,6′-dimethyltyrosine-l-tetrahydroisoquinoline-3-carboxylic acid [(2S,3R)TMT-l-Tic-OH] Is a Potent, Selective δ-Opioid Receptor Antagonist in Mouse Brain
The constrained opioid peptide (2S,3R)β-methyl-2′,6′-dimethyltyrosine-l-tetrahydroisoquinoline-3-carboxylic acid [(2S,3R)TMT-l-Tic-OH] exhibits high affinity and selectivity for the δ-opioidExpand
Inhibition of Improgan Antinociception by the Cannabinoid (CB)1 AntagonistN-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A): Lack of Obligatory Role for Endocannabinoids Acting at CB1 Receptors
Results show that SR141716A reduces improgan antinociception, but neither cannabinoids nor CB1 receptors seem to play an obligatory role in improgan signaling. Expand
Molecular interaction of the antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide with the CB1 cannabinoid receptor.
Results from conformational analyses, superimposition models, and 3D-QSAR models suggest that the N1 aromatic ring moiety of 1 dominates the steric binding interaction with the receptor in much the same way as does the C3 alkyl side chain of cannabinoid agonists and the C4 aroyl ring of the aminoalkylindole agonists. Expand


Cannabinoid receptor stimulation of guanosine-5'-O-(3-[35S]thio)triphosphate binding in rat brain membranes.
Results demonstrate that [35S]GTP gamma S binding in the presence of excess GDP is an effective measure of cannabinoid receptor coupling to G-proteins in brain membranes. Expand
Modulation by mu-opioid agonists of guanosine-5'-O-(3-[35S]thio)triphosphate binding to membranes from human neuroblastoma SH-SY5Y cells.
The ability of mu-opioid agonists to activate G proteins has been demonstrated by studying the binding of the GTP analogue guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTP gamma S) to membranesExpand
In vivo characterization of a specific cannabinoid receptor antagonist (SR141716A): inhibition of delta 9-tetrahydrocannabinol-induced responses and apparent agonist activity.
It is not clear whether this pharmacological activity represents an uncharacterized action of SR141716A, or an index of tonic activity of an endogenous cannabinergic system, but it will be useful in establishing the biochemical events responsible for the in vivo effects of exogenous cannabinoids, as well as inestablishing the existence of a putative endogenous cannabinoidergic system. Expand
SR 141716A, a cannabinoid receptor antagonist, produces hyperalgesia in untreated mice.
Results suggest that the cannabinoid system tonically regulates thermal nociceptive thresholds and the absence of this regulation results in hyperalgesia suggesting that hypoactivity of this system may be involved in certain types of chronic pain. Expand
SR141716A, a potent and selective antagonist of the brain cannabinoid receptor
SR141716A is the first selective and orally active antagonist of the brain cannabinoid receptor and should prove to be a powerful tool for investigating the in vivo functions of the anandamide/cannabinoid system. Expand