As chemical entities, lipoamino acids have been known for some time. However, more recently their occurrence and importance in mammalian species has been discovered. They appear to have close relationships with the endocannabinoids not only structurally but also in terms of biological actions. The latter include analgesia, anti-inflammatory effects, inhibition of cell proliferation and calcium ion mobilization. To date about 40 naturally occurring members of this family have been identified and, additionally, several synthetic analogs have been prepared and studied. To facilitate their identity, a nomenclature system has been suggested based on the name elmiric acid (EMA). The prototypic example, N-arachidonoyl glycine does not bind to CBI, however it does inhibit the glycine transporter GLYT2a and also appears to be a ligand for the orphan G-protein-coupled receptor GPRI8. It may also have a role in regulating tissue levels of anandamide by virtue of its inhibitory effect on FAAH the enzyme that mediates inactivation of anandamide. Its concentration in rat brain is several times higher than anandamide supporting its possible role as a physiological mediator. Future studies should be aimed at elucidating the actions of all of the members of this interesting family of molecules and gaining further insight into possible mechanisms of action. A promising use for these compounds would be as narcotic replacement agents.
There can be little doubt that there is an important unmet need for safe and effective non narcotic drugs to treat chronic pain/inflammatory conditions such as rheumatoid arthritis. As our population continues to attain greater longevity, this problem will likely be on the increase. While a number of agents are currently in use, they are either very expensive or have significant adverse effects such as the development of dependence. In many instances of intractable pain, patients are forced to turn to narcotic type analgesics for relief. The studies proposed in this request for support are aimed at discovering safe and relatively inexpensive drug candidates to treat this problem as well as a host of other types of inflammation and resulting pain. If successful, one important benefit would be a reduction in the use of addiction producing medications.
| Burstein, Sumner; McQuain, Catherine; Salmonsen, Rebecca et al. (2012) N-Amino acid linoleoyl conjugates: anti-inflammatory activities. Bioorg Med Chem Lett 22:872-5 |
| Burstein, Sumner H; McQuain, Catherine A; Ross, Alonzo H et al. (2011) Resolution of inflammation by N-arachidonoylglycine. J Cell Biochem 112:3227-33 |
