virodhamine and palmidrol

In this issue of the British Journal of Pharmacology, Ryberg et al. present convincing in vitro evidence that the orphan GPCR, GPR55, is a cannabinoid receptor. GPR55 was activated by a range of plant, synthetic and endogenous cannabinoids and blocked by the non-psychoactive phytocannabinoid, cannabidiol. Their experiments have revealed several differences between the pharmacology of GPR55 and the established cannabinoid CB1 and CB2 receptors. For example, the CB1 receptor antagonist, AM251, activated GPR55 and the main psychoactive constituent of cannabis, Delta9-tetrahydrocannabinol, displayed greater efficacy at GPR55 than at CB1 or CB2 receptors. They also compared the distribution of GPR55 and CB1 mRNA in mouse and report that GPR55 couples to Galpha13, that it is activated by virodhamine, palmitoylethanolamide and oleoylethanolamide, and that virodhamine displays relatively high efficacy as a GPR55 agonist. Still to be identified are the main roles played by GPR55 in health and disease and any potential therapeutic benefits of activating or blocking this receptor.

Topics: Amides; Animals; Arachidonic Acids; Cannabinoids; Dronabinol; Endocannabinoids; Ethanolamines; Humans; Oleic Acids; Palmitic Acids; Piperidines; Pyrazoles; Receptors, Cannabinoid; Receptors, G-Protein-Coupled

A simple and rapid analytical method is described for the simultaneous quantitative analysis of three different N-acylethanolamides in human biological samples: anandamide (AEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA). The method is based on a new hybrid solid phase extraction-precipitation technology followed by ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) analysis using d(4)-AEA as the internal standard. The method is linear up to 100ng/ml with a limit of quantitation of 50pg/ml for AEA and 100pg/ml for OEA and PEA. Good reproducibility, accuracy, and precision were demonstrated during the method validation. Application of this new methodology to the analysis of clinical study samples is presented.

Topics: Adolescent; Adult; Amides; Amidohydrolases; Arachidonic Acids; Calibration; Cannabinoids; Chromatography, High Pressure Liquid; Endocannabinoids; Enzyme Inhibitors; Ethanolamines; Female; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Molecular Structure; Oleic Acids; Palmitic Acids; Polyunsaturated Alkamides; Reproducibility of Results; Semen; Solid Phase Microextraction; Tandem Mass Spectrometry; Young Adult