AM4
Preliminary work with AM4 shows promise of being an effective treatment for multiple sclerosis, depression, fibromyalgia, erectile dysfunction, and memory impairment. The mechanism of action is unknown but appears to stimulate monoamine oxidase-A (MAO-A) gene expression and to reverse the inhibitory effects of alanine on MAO-A. MAO-A activity is necessary for the production of the catecholamine and indoleamine physiologically active aldehyde metabolites that are necessary for neurotransmission.
Research has proven that communication between cells is carried not only by the neurons and the astrocytes, but also via calcium and sodium ions in the extracellular medium [Fields, R.D. April 2004]. The extracellular fluid provides a bi-directional communication between the astrocytes and the neurons. The information highway between the pre and post synaptic neurons and the surrounding astrocytes is called the tripartite synapse and the information is carried by calcium and sodium ion transporters in the extracellular fluid [Fields, R.D. April 2004; Perea & Araque, 2005]. The movement of the ions in the extracellular fluid is dependent on entropy. Entropy is the movement of all spontaneous reactions toward a condition of greater randomness or greater disorder. Entropy involves the formation of a kosmotropic (highly structured environment) that dissociates to a chaotropic (disorderly environment) [Szent-Gyorgy, March 2005].
The side-chain carboxylate in proteins plays an integral part in forming and maintaining the extracellular medium in the tripartite synapse and the transmission of information via entropy. The side-chain carboxylate groups (i.e. aspartic and glutamic acids) in proteins contain two oxygen atoms that are nearer than occurs between water molecules in bulk liquid water (~2.82 Å). This normally causes a high density water clustering around these groups due to the closeness of the water molecules as they hydrogen bond to these carboxylate oxygen atoms. Such hydrogen bonding induces a more negative charge on the carboxyl oxygen atoms leading to an increase in the carboxylate pKa. It is found that Na+ ions prefer binding to the weaker carboxylate groups (pKa > 4.5) whereas K+ ions prefer the stronger acids (pKa < 3.5) [G. N. Ling, Life at the cell and below-cell level. The hidden history of a functional revolution in Biology, (Pacific Press, New York, 2001). ].
