The role of melatonin, neurokinin, neurotrophic tyrosine kinase and glucocorticoid receptors in antidepressant-like effect

Abstract

Over the last few decades, depression has become one of the major public health problems in our society. This problem is connected not only with morbidity, but also with treatment, specifically with the effectiveness of the therapy as well as the concomitant side effects of available antidepressants. Major depressive disorder is a complex clinical entity, including different molecular mechanisms and neurological processes. This complexity is a challenge for scientists seeking to discover an innovatory antidepressant drug with multiple and complementary mechanisms of action. In this review, we discuss the role of melatonin, neurokinin, neurotrophic tyrosine kinase and glucocorticoid receptors in depression and antidepressant-like effects.

Drug repurposing may generate novel approaches to treating depression

“…Mifepristone, glucocorticoid receptor antagonist, has been investigated for its effects on psychiatric disorders including depression . Further, melatonin receptor activation has recently been implicated in the treatment of depression . For example, clinically approved antidepressant drug agomelatine stimulates G‐protein‐coupled melatonin receptors 1 and 2, thereby improving mood status in patients with MDD .…”

“…For example, clinically approved antidepressant drug agomelatine stimulates G‐protein‐coupled melatonin receptors 1 and 2, thereby improving mood status in patients with MDD . On the other hand, neurokinin receptor antagonism demonstrated antidepressant effects . Neurokinins including substance P, neurokinin A and neurokinin B are excitatory neurotransmitters which exert their pharmacological actions through G‐protein‐coupled neurokinin 1, 2 and 3 receptors, respectively .…”

“…Aprepitant which blocks neurokinin 1 receptors had been found to stand as a promising antidepressant drug in early clinical studies, but its week efficacy resulted in not approving it for treating MDD . The neurotrophic theory has been suggested to explain why depression could develop and how antidepressant drugs improve depressed mood . Markers of neuroplasticity, including brain‐derived neurotrophic factor and its downstream regulator cyclic AMP response element binding protein, have been found to be implicated in rats exhibiting depression‐like behaviour .…”

“…[19] Further, melatonin receptor activation has recently been implicated in the treatment of depression. [20] For example, clinically approved antidepressant drug agomelatine stimulates G-protein-coupled melatonin receptors 1 and 2, thereby improving mood status in patients with MDD. [21] On the other hand, neurokinin receptor antagonism demonstrated antidepressant effects.…”

“…[20] Neurokinins including substance P, neurokinin A and neurokinin B are excitatory neurotransmitters which exert their pharmacological actions through G-protein-coupled neurokinin 1, 2 and 3 receptors, respectively. [20] Aprepitant which blocks neurokinin 1 receptors had been found to stand as a promising antidepressant drug in early clinical studies, [22] but its week efficacy resulted in not approving it for treating MDD. [23] The neurotrophic theory has been suggested to explain why depression could develop and how antidepressant drugs improve depressed mood.…”