Agonist-antagonist characterization of 6'-cyanohex-2'-yne-Delta(8)-tetrahydrocannabinol in two isolated tissue preparations

Roger Guy Pertwee, S R Fernando, G Griffin, W Ryan, R K Razdan, D R Compton, Martin Billy R.

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Abstract

This investigation was directed at characterizing some of the pharmacological 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 partial cannabinoid CB1 receptor agonist (EC(50) - 0.015 nM). In the guinea-pig myenteric plexus preparation, it antagonized WIN 55,212-2 {(R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholino-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone} and CP 55,940 {(-)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol} with K-d values of 0.65 and 0.27 nM, respectively. After in vivo Delta(9)-tetrahydrocannabinol pretreatment, the sensitivity of vasa deferentia to 0-823-induced inhibition of electrically evoked contractions was reduced by 127-fold. 3.162 nM O-823 was inhibitory in unpretreated vasa deferentia but antagonized 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)-tetrahydrocannabinol pretreated vasa deferentia but a partial agonist in unpretreated vasa deferentia because the first two of these preparations contain fewer receptors than the third.

Original languageEnglish
Pages (from-to)195-201
Number of pages7
JournalEuropean Journal of Pharmacology
Volume315
Issue number2
DOIs
Publication statusPublished - 14 Nov 1996

Keywords

  • cannabinoid receptor antagonist
  • cannabinoid receptor partial agonist
  • 6'-cyanohex-2'-yne-Delta(8)-tetrahydrocannabinol 0-823
  • SR141716A
  • vas deferens, mouse
  • myenteric plexus longitudinal muscle preparation
  • small intestine, guinea-pig
  • CANNABINOID RECEPTOR
  • RAT-BRAIN
  • VAS-DEFERENS
  • BINDING
  • DELTA-9-TETRAHYDROCANNABINOL
  • Cannabinoid receptor antagonist
  • Cannabinoid receptor partial agonist
  • 6'-Cyanohex-2'-yne-¿8-tetrahydrocannabinol
  • O-823
  • Vas deferens
  • mouse
  • Myenteric plexus-longitudinal muscle preparation
  • small intestine
  • guinea-pig

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