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Review
. 2023 Apr 27;13(5):734.
doi: 10.3390/brainsci13050734.

Agomelatine: A Potential Multitarget Compound for Neurodevelopmental Disorders

Rosa Savino  1 , Anna Nunzia Polito  1 , Gabriella Marsala  2 , Antonio Ventriglio  3 , Melanie Di Salvatore  1 , Maria Ida De Stefano  3 , Anna Valenzano  3 , Luigi Marinaccio  3 , Antonello Bellomo  3 , Giuseppe Cibelli  3 , Marcellino Monda  4 , Vincenzo Monda  5 , Antonietta Messina  4 , Rita Polito  3 , Marco Carotenuto  6 , Giovanni Messina  3
Affiliations
Review

Agomelatine: A Potential Multitarget Compound for Neurodevelopmental Disorders

Rosa Savino et al. Brain Sci. .

Abstract

Agomelatine (AGM) is one of the latest atypical antidepressants, prescribed exclusively for the treatment of depression in adults. AGM belongs to the pharmaceutical class of melatonin agonist and selective serotonin antagonist ("MASS"), as it acts both as a selective agonist of melatonin receptors MT1 and MT2, and as a selective antagonist of 5-HT2C/5-HT2B receptors. AGM is involved in the resynchronization of interrupted circadian rhythms, with beneficial effects on sleep patterns, while antagonism on serotonin receptors increases the availability of norepinephrine and dopamine in the prefrontal cortex, with an antidepressant and nootropic effect. The use of AGM in the pediatric population is limited by the scarcity of data. In addition, few studies and case reports have been published on the use of AGM in patients with attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Considering this evidence, the purpose of this review is to report the potential role of AGM in neurological developmental disorders. AGM would increase the expression of the cytoskeleton-associated protein (ARC) in the prefrontal cortex, with optimization of learning, long-term memory consolidation, and improved survival of neurons. Another important feature of AGM is the ability to modulate glutamatergic neurotransmission in regions associated with mood and cognition. With its synergistic activity a melatoninergic agonist and an antagonist of 5-HT2C, AGM acts as an antidepressant, psychostimulant, and promoter of neuronal plasticity, regulating cognitive symptoms, resynchronizing circadian rhythms in patients with autism, ADHD, anxiety, and depression. Given its good tolerability and good compliance, it could potentially be administered to adolescents and children.

Keywords: AGM; attention deficit hyperactivity disorder (ADHD); autism spectrum disorder (ASD); melatonin agonist and selective serotonin antagonist (MASS); neurodevelopmental disorders.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Dark/light signaling, melatonin synthesis.
Figure 2
Figure 2
Melatonin antioxidant properties and tryptophan metabolic pathway.
See this image and copyright information in PMC

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