Agomelatine, a melatonin agonist with antidepressant properties.

University at Buffalo, Department of Psychiatry, 462 Grider St, Buffalo NY 14215, USA.
Expert Opinion on Investigational Drugs (Impact Factor: 4.74). 10/2009; 18(10):1533-40. DOI: 10.1517/13543780903292634
Source: PubMed

ABSTRACT Agomelatine (beta-methyl-6-chloromelatonin), which is structurally homologous to melatonin, is a potent agonist of melatonin MT1 and MT2 receptors as well as an antagonist of serotonin 5-HT(2C) receptors. Agomelatine appears to improve sleep without causing daytime sedation. It has not been found to be associated with sexual side effects and discontinuation symptoms. Three placebo-controlled trials, one of them a dose finding study and two of them pivotal trials, suggest that agomelatine is an antidepressant at doses of 25 - 50 mg/day. Agomelatine appears to be well tolerated, without sexual or cardiac adverse effects, weight gain or discontinuation syndromes. Animal studies suggest a possible neuroprotective action of agomelatine, although there are more data in favor of an anxiolytic effect. Substantially more research is needed to establish its role in the treatment of mood and circadian rhythm disorders.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Agomelatine is a novel antidepressant drug with melatonin receptor agonist and 5-HT(2C) receptor antagonist properties. We analyzed whether agomelatine has antioxidant properties. Antioxidant activity of agomelatine (25, 50, or 75 mg/kg, i.p.) or melatonin (50 mg/kg) was investigated by measuring lipid peroxidation levels, nitrite content, and catalase activities in the prefrontal cortex, striatum, and hippocampus of Swiss mice pentylenetetrazole (PTZ) (85 mg/kg, i.p.), pilocarpine (400 mg/kg, i.p.), picrotoxin (PTX) (7 mg/kg, i.p.), or strychnine (75 mg/kg, i.p.) induced seizure models. In the pilocarpine-induced seizure model, all dosages of agomelatine or melatonin showed a significant decrease in TBARS levels and nitrite content in all brain areas when compared to controls. In the strychnine-induced seizure model, all dosages of agomelatine and melatonin decreased TBARS levels in all brain areas, and agomelatine at low doses (25 or 50 mg/kg) and melatonin decreased nitrite contents, but only agomelatine at 25 or 50 mg/kg showed a significant increase in catalase activity in three brain areas when compared to controls. Neither melatonin nor agomelatine at any dose have shown no antioxidant effects on parameters of oxidative stress produced by PTX- or PTZ-induced seizure models when compared to controls. Our results suggest that agomelatine has antioxidant activity as shown in strychnine- or pilocarpine-induced seizure models.
    Cellular and Molecular Neurobiology 06/2013; · 2.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Several melatonin receptors agonists (ramelteon, prolonged-release melatonin, agomelatine and tasimelteon) have recently become available for the treatment of insomnia, depression and circadian rhythms sleep-wake disorders. The efficacy and safety profiles of these compounds in the treatment of the indicated disorders are reviewed. Accumulating evidence indicates that sleep-wake disorders and co-existing medical conditions are mutually exacerbating. This understanding has now been incorporated into the new Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Therefore, when evaluating the risk/benefit ratio of sleep drugs, it is pertinent to also evaluate their effects on wake and comorbid condition. Beneficial effects of melatonin receptor agonists on comorbid neurological, psychiatric, cardiovascular and metabolic symptomatology beyond sleep regulation are also described. The review underlines the beneficial value of enhancing physiological sleep in comorbid conditions.
    International Journal of Molecular Sciences 09/2014; 15(9):15924-15950. · 2.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent chronobiological studies show that drug consumption has a negative effect on circadian rhythmic expression. Circadian rhythm may even disappear in extreme cases, which suggests a lesser quality of the wake and sleep periods. Moreover, some circadian genes (Clock, Period) may be involved as biological risk factors in drug addictions. At the same time, the modification of their genetic expression has been found in patients with addiction disorders. Evening circadian typology is currently being considered as a risk factor in the onset and maintenance of drug consumption, while the morning typology appears to be a protection factor. The circadian genes are also related to psychopathologies such as mood disorders, and in the future, their implication in dual pathology should be further studied. Preventive and therapeutic approaches to addiction should take into account circadian rhythmic organization. In many cases, it may suffice to establish regular time patterns of wake–sleep, meals and daily activity with a tendency towards a morningness pattern of functioning. Other strategies, such as light therapy and melatonin administration, may be applied for long periods of time, since they have shown an excellent degree of security, and may also be a protective measure against relapse or the appearance of neuropsychiatric symptoms.
    Journal of Substance Use 06/2013; 18(3):171-183. · 0.48 Impact Factor