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.

Research output: Contribution to journalArticle

40 Citations (Scopus)

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

Cite this

Agonist-antagonist characterization of 6'-cyanohex-2'-yne-Delta(8)-tetrahydrocannabinol in two isolated tissue preparations. / Pertwee, Roger Guy; Fernando, S R ; Griffin, G ; Ryan, W ; Razdan, R K ; Compton, D R ; Billy R., Martin.

In: European Journal of Pharmacology, Vol. 315, No. 2, 14.11.1996, p. 195-201.

Research output: Contribution to journalArticle

Pertwee, Roger Guy ; Fernando, S R ; Griffin, G ; Ryan, W ; Razdan, R K ; Compton, D R ; Billy R., Martin. / Agonist-antagonist characterization of 6'-cyanohex-2'-yne-Delta(8)-tetrahydrocannabinol in two isolated tissue preparations. In: European Journal of Pharmacology. 1996 ; Vol. 315, No. 2. pp. 195-201.
@article{b771d3868ff94644861f4825a5c43080,
title = "Agonist-antagonist characterization of 6'-cyanohex-2'-yne-Delta(8)-tetrahydrocannabinol in two isolated tissue preparations",
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.",
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",
author = "Pertwee, {Roger Guy} and Fernando, {S R} and G Griffin and W Ryan and Razdan, {R K} and Compton, {D R} and {Billy R.}, Martin",
year = "1996",
month = "11",
day = "14",
doi = "10.1016/S0014-2999(96)00631-0",
language = "English",
volume = "315",
pages = "195--201",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Agonist-antagonist characterization of 6'-cyanohex-2'-yne-Delta(8)-tetrahydrocannabinol in two isolated tissue preparations

AU - Pertwee, Roger Guy

AU - Fernando, S R

AU - Griffin, G

AU - Ryan, W

AU - Razdan, R K

AU - Compton, D R

AU - Billy R., Martin

PY - 1996/11/14

Y1 - 1996/11/14

N2 - 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.

AB - 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.

KW - cannabinoid receptor antagonist

KW - cannabinoid receptor partial agonist

KW - 6'-cyanohex-2'-yne-Delta(8)-tetrahydrocannabinol 0-823

KW - SR141716A

KW - vas deferens, mouse

KW - myenteric plexus longitudinal muscle preparation

KW - small intestine, guinea-pig

KW - CANNABINOID RECEPTOR

KW - RAT-BRAIN

KW - VAS-DEFERENS

KW - BINDING

KW - DELTA-9-TETRAHYDROCANNABINOL

KW - Cannabinoid receptor antagonist

KW - Cannabinoid receptor partial agonist

KW - 6'-Cyanohex-2'-yne-¿8-tetrahydrocannabinol

KW - O-823

KW - Vas deferens

KW - mouse

KW - Myenteric plexus-longitudinal muscle preparation

KW - small intestine

KW - guinea-pig

U2 - 10.1016/S0014-2999(96)00631-0

DO - 10.1016/S0014-2999(96)00631-0

M3 - Article

VL - 315

SP - 195

EP - 201

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 2

ER -