6″-Azidohex-2″-yne-cannabidiol

A potential neutral, competitive cannabinoid CB1 receptor antagonist

Adèle Thomas, Ruth A. Ross, Bijali Saha, Anu Mahadevan, Raj K. Razdan, Roger G. Pertwee*

*Corresponding author for this work

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Previous experiments with the mouse vas deferens have shown that cannabidiol produces surmountable antagonism of cannabinoid CB1 receptor agonists at concentrations well below those at which it binds to cannabinoid CB1 receptors and antagonizes α1- adrenoceptor agonists insurmountably. It also enhances electrically evoked contractions of this tissue. We have now found that subtle changes in the structure of cannabidiol markedly influence its ability to produce each of these effects, suggesting the presence of specific pharmacological targets for this non-psychoactive cannabinoid. Our experiments were performed with cannabidiol, 6-azidohex-2-yne-cannabidiol, abnormal-cannabidiol and 2′-monomethoxy- and 2′,6′-dimethoxy-cannabidiol. Of these, 6-azidohex-2-yne-cannabidiol was as potent as cannabidiol in producing surmountable antagonism of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (R-(+)-WIN55212) in vasa deferentia. However, it produced this antagonism with a potency that matched its cannabinoid CB1 receptor affinity, suggesting that, unlike cannabidiol, it is a competitive cannabinoid CB1 receptor antagonist. Moreover, since it did not enhance the amplitude of electrically evoked contractions, it may be a neutral cannabinoid CB1 receptor antagonist.

Original languageEnglish
Pages (from-to)213-221
Number of pages9
JournalEuropean Journal of Pharmacology
Volume487
Issue number1-3
DOIs
Publication statusPublished - 8 Mar 2004
Externally publishedYes

    Fingerprint

Keywords

  • Abnormal-cannabidiol
  • Cannabidiol
  • Cannabinoid CB receptor
  • Mouse vas deferens
  • Novel cannabinoid receptor antagonist
  • WIN55212

Cite this