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• W1786879564 abstract "Background and purpose:To follow up in vitro evidence that Δ9-tetrahydrocannabivarin extracted from cannabis (eΔ9-THCV) is a CB1 receptor antagonist by establishing whether synthetic Δ9-tetrahydrocannabivarin (O-4394) and Δ8-tetrahydrocannabivarin (O-4395) behave as CB1 antagonists in vivo.Experimental approach:O-4394 and O-4395 were compared with eΔ9-THCV as displacers of [3H]-CP55940 from specific CB1 binding sites on mouse brain membranes and as antagonists of CP55940 in [35S]GTPγS binding assays performed with mouse brain membranes and of R-(+)-WIN55212 in mouse isolated vasa deferentia. Their ability to antagonize in vivo effects of 3 or 10 mg kg−1 (i.v.) Δ9-tetrahydrocannabinol in mice was then investigated.Key results:O-4394 and O-4395 exhibited similar potencies to eΔ9-THCV as displacers of [3H]-CP55940 (Ki=46.6 and 64.4 nM, respectively) and as antagonists of CP55940 in the [35S]GTPγS binding assay (apparent KB=82.1 and 125.9 nM, respectively) and R-(+)-WIN55212 in the vas deferens (apparent KB=4.8 and 3.9 nM respectively). At i.v. doses of 0.1, 0.3, 1.0 and/or 3 mg kg−1 O-4394 and O-4395 attenuated Δ9-tetrahydrocannabinol-induced anti-nociception (tail-flick test) and hypothermia (rectal temperature). O-4395 but not O-4394 also antagonized Δ9-tetrahydrocannabinol-induced ring immobility. By themselves, O-4395 and O-4394 induced ring immobility at 3 or 10 mg kg−1 (i.v.) and antinociception at doses above 10 mg kg−1 (i.v.). O-4395 also induced hypothermia at 3 mg kg−1 (i.v.) and above.Conclusions and implications:O-4394 and O-4395 exhibit similar in vitro potencies to eΔ9-THCV as CB1 receptor ligands and as antagonists of cannabinoid receptor agonists and can antagonize Δ9-tetrahydrocannabinol in vivo.British Journal of Pharmacology (2007) 150, 586–594. doi:10.1038/sj.bjp.0707124" @default.
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• W1786879564 date "2007-03-01" @default.
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• W1786879564 title "The psychoactive plant cannabinoid, Δ⁹ -tetrahydrocannabinol, is antagonized by Δ⁸ - and Δ⁹ -tetrahydrocannabivarin in mice <i>in vivo</i>" @default.
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• W1786879564 doi "https://doi.org/10.1038/sj.bjp.0707124" @default.
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