The pharmacological properties of antidepressants

Abstract

Antidepressant drugs represent one of the main forms of effective treatment for the amelioration of depressive symptoms. Most available antidepressants increase extracellular levels of monoamines. However, it is now recognized that monoamine levels and availability are only part of the story, and that antidepressants whose mechanism of action is mainly based on the modulation of monoaminergic systems may not be able to satisfy the unmet needs of depression. Therefore, a number of compounds, developed for their potential antidepressant activity, are endowed with putative mechanisms of action not affecting traditional monoamine targets. This article briefly reviews, within a mechanistic perspective, the pharmacological profiles of representative antidepressants from each class, including monoamine oxidase inhibitors, tricyclics, norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, norepinephrine and serotonin reuptake inhibitors, antidepressants interacting with dopaminergic, melatonergic, glutamatergic, or neuropeptide systems. The undesirable side effects of currently used antidepressants, which can often be a reason for lack of compliance, are also considered.

Antidepressant-like effect of quercetin in bulbectomized mice and involvement of the antioxidant defenses, and the glutamatergic and oxidonitrergic pathways

“…This disease is a chronic mental disorder, and in some cases, is a potentially fatal disorder, representing a serious public health problem that generates high costs to society (Fleck et al, 2009) and that strongly affects quality of life of the patients (Larsen et al, 2010;Van Der Feltz-Cornelis et al, 2010). It is wellestablished that depression involves a reduction in the monoamine system, particularly in the neurotransmission of serotonin, dopamine and norepinephrine, or impaired activity of their receptors (Racagni and Popoli, 2010). In summary, the center of action of current drug therapy is to correct monoamine deficits by increasing synaptic concentrations (Higgins and George, 2010;Bennabi et al, 2015).…”

Inhibitory effect of the antidepressant imipramine on NF-κB-dependent CXCL1 expression in TNFα-exposed astrocytes

“…1) that inhibits 5-hydroxytryptamine (serotonin) and norepinephrine reuptake [7]. Imipramine is one of the most effective drugs in the treatment of severe chronic depression [8].…”

Glutamate hypothesis of depression and its consequences for antidepressant treatments

“…However, these drugs have significant limitations, including a long time lag for therapeutic response (weeks to months), low response rates and side effects serious enough to induce discontinuation in nearly 20% of patients. Moreover, the delayed response is suggestive of an involvement in antidepressant therapeutic action of slow-onset adaptations in downstream signaling pathways regulating neuroplasticity and cellular resilience [2,3].…”

“…However, these drugs have significant limitations, including a long time lag for therapeutic response (weeks to months), low response rates and side effects serious enough to induce discontinuation in nearly 20% of patients. Moreover, the delayed response is suggestive of an involvement in antidepressant therapeutic action of slow-onset adaptations in downstream signaling pathways regulating neuroplasticity and cellular resilience [2,3].Recent growing evidence suggests that glutamatergic neurotransmission, the major excitatory system in the brain, plays a critical role in the pathophysiology and treatment of neuropsychiatric disorders. The glutamatergic system is interconnected with GABAergic and monoaminergic pathways, and it has been shown that approximately 80% of neurons in the neocortex are excitatory glutamatergic neurons [4].…”