CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 6, Issue 2, 2007

Depressive illness is a devastating disorder that affects 18.8 million American adults (9.5% of the adult population) and is the leading cause of disability in the U.S. and other developed countries. Depression occurs twice as frequently in women relative to men. When untreated, depressive episodes increase in severity and frequency, and can lead to suicide. The symptoms of major depressive disorder include sad or irritable Read More

Current treatments for depression are less than optimal in terms of onset of action, response and remission rates, and side-effect profiles. Glutamate is the major excitatory neurotransmitter controlling synaptic excitability and plasticity in most brain circuits, including limbic pathways involved in depression. Thus, drugs that target glutamate neuronal transmission offer novel approaches to treat depression. Recently, th Read More

Ample evidence indicates that glutamate homeostasis and neurotransmission are disrupted in major depressive disorder; but the nature of this disruption and the mechanisms by which it contributes to the syndrome are unclear. Likewise, the effect of existing antidepressants on glutamate is unclear, as is the potential of drugs directly targeting glutamatergic neurotransmission to act as novel antidepressant medications. Thes Read More

There is an increasing body of evidence implicating a role for α-amino-3-hydroxy-5-methyl-4 isoxazoleproprionic acid (AMPA) receptors in major depression and in the actions of antidepressant drugs. Alterations in AMPA receptors and other ionotropic glutamate receptors have been reported in depression, and following antidepressant treatment. Compounds which augment signaling through AMPA receptors (AMPA receptor p Read More

Increasing evidence suggests that abnormalities in amino neurotransmission are associated with the neurobiology of depression. Preclinical studies demonstrate that GABA modulating agents are active in commonly used rodent behavioral models of antidepressant activity, and that chronic administration of antidepressant drugs induces marked changes in GABAergic function. In humans, depressed patients have lower plas Read More

The majority of antidepressants in current use inhibit the uptake of serotonin and/or norepinephrine. Drugs inhibiting the uptake of serotonin, norepinephrine and dopamine (triple reuptake inhibitors) may offer therapeutic advantages compared to single and/or dual reuptake inhibitors. This review provides a rationale for developing this class of compound and describes the results of preclinical and clinical studies with a famil Read More

Preclinical and clinical studies have demonstrated that stress and depression result in cell atrophy and loss in limbic and cortical brain regions while antidepressants reverse these effects. In concert with these findings, reduced expression of numerous genes that mediate neurotrophin and growth factor signaling has been observed in depressed patients and in stressed animals. Further, antidepressants are known to elevate Read More