Description
R-1 methanandamide is a potent cannabinoid (CB) receptor 1 agonist in the methanandamide series. It is selective for CB1 over CB2 receptors with Ki values ranging from 17.9 to 28.3 and 815 to 868 nM, respectively. R-1 methanandamide is more potent than arachidonoyl ethanolamide (AEA; ). In addition, R-1 methanandamide is more resistant than AEA to hydrolytic inactivation by fatty acid amide hydrolase (FAAH).
Uses
Methanandamide is a metabolically stable endocannabinoid analogue of the mammalian brain ligand Anandamide. Methanandamide is known to improve myocardial resistance against arrhythmogenic effects and can also be used to modulate behaviors caused by Amphetamine (HCl: A634248).
Definition
ChEBI: Methanandamide is a fatty amide.
Biological Activity
Stable anandamide analog that is a selective agonist for the CB 1 receptor (K i values are 20 and 815 nM for CB 1 and CB 2 receptors respectively). Also displays agonist activity at vanilloid receptors. Also available in water-soluble emulsion ((R)-N-(2-Hydroxy-1-methylethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide ) and as part of the Cannabinoid CB 1 Receptor Tocriset™ .
Biochem/physiol Actions
R(+)-Methanandamide is metabolically stable congener of anandamide that has higher affinity for the cannabinoid receptor. Of the analogs tested, (R)-methanandamide exhibited the highest affinity for the cannabinoid receptor with a Ki of 20 +/- 1.6 nM, 4-fold lower than that of anandamide (Ki = 78 +/- 2 nM). (R)-methanandamide exhibits high stability to aminopeptidase hydrolysis. Experiments with mice have demonstrated that (R)-methanandamide also posseses cannabimimetric properties in vivo, as established by the four tests of hypothermia, hypokinesia, ring immobility, and antinociception.
References
[1] PERTWEE R. Pharmacology of Cannabinoid Receptor Ligands[J]. Current medicinal chemistry, 1999, 1 1. DOI:
10.2174/0929867306666220401124036[2] VASILIKI ABADJI. (R)-Methanandamide: A Chiral Novel Anandamide Possessing Higher Potency and Metabolic Stability[J]. Journal of Medicinal Chemistry, 1994, 37 12: 1889-1893. DOI:
10.1021/jm00038a020
