text: Cannabinoid discrimination and antagonism by CB(1) neutral and inverse agonist antagonists.
  Cannabinoid receptor 1 (CB(1)) inverse agonists (e.g., rimonabant) have been reported to produce adverse effects including nausea, emesis, and anhedonia that limit their clinical applications. Recent laboratory studies suggest that the effects of CB(1) neutral antagonists differ from those of such inverse agonists, raising the possibility of improved clinical utility. However, little is known regarding the antagonist properties of neutral antagonists. In the present studies, the CB(1) inverse agonist SR141716A (rimonabant) and the CB(1) neutral antagonist AM4113 were compared for their ability to modify CB(1) receptor-mediated discriminative stimulus effects in nonhuman primates trained to discriminate the novel CB(1) full agonist AM4054. Results indicate that AM4054 serves as an effective CB(1) discriminative stimulus, with an onset and time course of action comparable with that of the CB(1) agonist Δ(9)-tetrahydrocannabinol, and that the inverse agonist rimonabant and the neutral antagonist AM4113 produce dose-related rightward shifts in the AM4054 dose-effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of AM4054. Schild analyses further show that rimonabant and AM4113 produce highly similar antagonist effects, as evident in comparable pA(2) values (6.9). Taken together with previous studies, the present data suggest that the improved safety profile suggested for CB(1) neutral antagonists over inverse agonists is not accompanied by a loss of antagonist action at CB(1) receptors.
entities.id: T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T25 T26 T27 T2 T3 T4 T5 T6 T7 T8 T9
entities.type: CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-N GENE-N CHEMICAL GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
entities.text: AM4113 AM4054 AM4054 Δ(9)-tetrahydrocannabinol rimonabant Cannabinoid Cannabinoid receptor 1 CB(1) CB(1) receptors CB(1) Cannabinoid CB(1) CB(1) CB(1) CB(1) receptor CB(1) CB(1) CB(1) CB(1) AM4113 AM4054 AM4054 rimonabant AM4113 SR141716A rimonabant rimonabant