New Molecular Therapeutic Approaches

Based on extensive new information as to the cautions that need to be employed in the use of the standard and SRI antidepressant classes, there is an urgent need for new classes of antidepressant thymoleptics.  One such agent, ALCAR (ALCAR Model), has a body of literature that supports the possibility of its therapeutic value in a number of depressive categories.

In a very preliminary study of two geriatric depressed individuals, ALCAR was shown to reverse alterations in brain membrane phospholipid and high-energy phosphate metabolism which correlated with clinical improvement (Neuromolecular Brain Changes) (Pettegrew et al, 2002).  Specifically, ALCAR reduced the levels of PME(s-t_c) which include the membrane phospholipids building blocks phosphocholine, phosphoethanolamine, and phosphoserine and the phosphatidylinositol cycle intermediate myo-inositol-1-phosphate. Reduction in the levels of PME(s-t_c) correlated with clinical improvement over the 12 weeks of the study.  Additionally, ALCAR increased the levels of the high-energy phosphate buffer, phosphocreatine, over the 12 weeks of study which also correlated with clinical improvement.  It is of considerable interest that ALCAR reduced the levels of PME(s-t_c) and Li⁺ has been shown to increase the levels of PME(s-t_c), especially the levels of myo-inositol-1-phosphate.  Therefore ALCAR apparently improves brain function by a mechanism different from that of Li⁺.

Maintenance therapy with ALCAR might play a role in preventing the reoccurrence of severe depression in the elderly and thereby reduce the risk of suicide.  Because of the wide safety margin for ALCAR, it would likely find physician acceptance in primary care settings. This is especially important given the known narrow therapeutic window for Li⁺ and its known toxicity.