AGOMELATINE IS A MELATONERGIC ANTIDEPRESSANT WHICH HAS NO DISCONTINUATION SYNDROME AND HAVE NO SEXUAL SIDE EFFECTS COMPARED TO SSRIS, SNRIS AND THE OLDER TRICYCLIC ANTIDEPRESSANTS. AGOMELATINE MAY ALSO HAVE POSITIVE EFFECTS ON SLEEP.
AGOMELATINE IS A MELATONIN RECEPTOR AGONIST AND A 5-HT RECEPTOR ANTAGONIST. BINDING STUDIES INDICATE THAT IT HAS NO EFFECT ON MONOAMINE UPTAKE AND NO AFFINITY FOR ADRENERGIC, HISTAMINERGIC, CHOLINERGIC, DOPAMINERGIC AND BENZODIAZEPINE RECEPTORS, NOR OTHER SEROTONERGIC RECEPTORS.
AGOMELATINE RESYNCHRONISES CIRCADIAN RHYTHMS IN ANIMAL MODELS OF DELAYED SLEEP PHASE SYNDROME. BY ANTAGONIZING 5-HT2C RECEPTORS, IT DISINHIBITS/INCREASES NORADRENALINE AND DOPAMINE RELEASE SPECIFICALLY IN THE FRONTAL CORTEX. THEREFORE, IT IS SOMETIMES CLASSIFIED AS A NOREPINEPHRINE-DOPAMINE DISINHIBITOR. IT HAS NO INFLUENCE ON THE EXTRACELLULAR LEVELS OF SEROTONIN. IN HUMANS, AGOMELATINE HAS POSITIVE PHASE SHIFTING PROPERTIES; IT INDUCES A PHASE ADVANCE OF SLEEP, BODY TEMPERATURE DECLINE AND MELATONIN ONSET. ADDITIONALLY, POSSIBLY BECAUSE OF ITS ACTION ON MELATONIN RECEPTORS, AGOMELATINE APPEARS TO IMPROVE SLEEP QUALITY, WITH NO REPORTED DAYTIME DROWSINESS.