Novel adamantyl cannabinoids as CB1 receptor probes.

Journal Article (Journal Article)

In previous studies, compound 1 (AM411), a 3-(1-adamantyl) analogue of the phytocannabinoid (-)-Δ(8)-tetrahydrocannabinol (Δ(8)-THC), was shown to have improved affinity and selectivity for the CB1 receptor. In this work, we further explored the role of the 1-adamantyl group at the C-3 position in a series of tricyclic cannabinoid analogues modified at the 9-northern aliphatic hydroxyl (NAH) position. Of these, 9-hydroxymethyl hexahydrocannabinol 11 (AM4054) exhibited high CB1 affinity and full agonist profile. In the cAMP assay, the 9-hydroxymethyl cannabinol analogue 24 (AM4089) had a partial agonist profile, with high affinity and moderate selectivity for rCB1 over hCB2. In vivo results in rat models of hypothermia and analgesia were congruent with in vitro data. Our in vivo data indicate that 3-(1-adamantyl) substitution, within NAH cannabinergics, imparts improved pharmacological profiles when compared to the corresponding, traditionally used 3-dimethylheptyl analogues and identifies 11 and 24 as potentially useful in vivo CB1 cannabinergic probes.

Full Text

Duke Authors

Cited Authors

  • Thakur, GA; Bajaj, S; Paronis, C; Peng, Y; Bowman, AL; Barak, LS; Caron, MG; Parrish, D; Deschamps, JR; Makriyannis, A

Published Date

  • May 23, 2013

Published In

Volume / Issue

  • 56 / 10

Start / End Page

  • 3904 - 3921

PubMed ID

  • 23621789

Pubmed Central ID

  • PMC3706088

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

Digital Object Identifier (DOI)

  • 10.1021/jm4000775


  • eng

Conference Location

  • United States