AGONIST-ANTAGONIST CHARACTERIZATION OF 6'-CYANOHEX-2'-YNE-DELTA(8)-TETRAHYDROCANNABINOL IN 2 ISOLATED TISSUE PREPARATIONS

This investigation was directed at characterizing some of the pharmaco logical properties of 6'-cyanohex-2'-yne-Delta(8)-tetrahydrocannabinol (0-823), a compound with high affinity for cannabinoid binding sites (K-i = 0.77 nM). In mouse vasa deferentia, 0-823 behaved as a potent p artial cannabinoid CB1 receptor agonist (EC(50) - 0.015 nM). In the gu inea-pig myenteric plexus preparation, it antagonized WIN 55,212-2 2,3 -de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone} and CP 55,940 heptyl)p henyl]-4-(3-hydroxypropyl)cyclohexan-1-ol} with K-d values of 0.65 and 0.27 nM, respectively. After in vivo Delta(9)-tetrahydrocannabinol pr etreatment, the sensitivity of vasa deferentia to 0-823-induced inhibi tion of electrically evoked contractions was reduced by 127-fold. 3.16 2 nM O-823 was inhibitory in unpretreated vasa deferentia but antagoni zed CP 55,940 in pretreated tissues (K-d = 0.26 nM). O-823 is probably an antagonist in the myenteric plexus preparation and Delta(9)-tetrah ydrocannabinol pretreated vasa deferentia but a partial agonist in unp retreated vasa deferentia because the first two of these preparations contain fewer receptors than the third.