2-Palmitoyl glycerol (2-PG) has been isolated along with the potent endocannabinoid 2-arachidonoyl glycerol (2-AG) from various tissues. Although 2-PG displays no intrinsic agonist activity on CB1 or CB2 receptors, it does potentiate the ability of 2-AG to inhibit adenylyl cyclase. 2-PG also potentiates the analgesic, hypokinetic, and anxiolytic effects of 2-AG in mice. This “entourage” effect has been attributed to the ability of compounds such as 2-PG to inhibit reuptake and/or compete with the active endocannabinoids for access to inactivating enzymes such as FAAH and monoglyceride lipase. Palmitoyl serinol is a stable analog of 2-PG bearing an amide linkage in place of the labile glyceryl ester. This has the potential to enhance its “entourage” activities as a result of a prolonged in vivo half-life. Palmitoyl serinol is also an analog of C-16 ceramide. Incubation of neuroblastoma cells with palmitoyl serinol causes apoptosis with an IC50 of approximately 80 μM.
