Does agomelatine block 5-HT2C receptors in humans?

Abstract

receptor antagonist properties to healthy volunteersproduces reliable increases in slow wave sleep (SWS) in thepolysomnogram (see Sharpley et al. 1994; Sharpley andCowen 1995). The aim of the present study was to test thehypothesis that agomelatine would also increase SWS inhumans.We studied 15 healthy subjects (eight female, sevenmale; mean age 25.9 years, range 19–47 years) who weredetermined by clinical interview (non-patient version of theStructured Clinical Interview for DSM-IV) to have nocurrent history of psychiatric disorder or sleep disorder andwho were not taking any other medication. Each subjecttook matching capsules of placebo and agomelatine(25 mg) once, orally, 30 min before retiring to sleep in adouble blind, balanced order, crossover design with a 7- to14-day washout period between each sleep polysomno-gram. Subjective ratings of sleep (on a five-point scale) andside effects (on a four-point scale) were elicited themorning after each sleep study.On each study night, polysomnograms were recorded aseach participant slept at home, using the Embla A10 digitaldata recording system (Medcare, Broomfield, CO, USA).Participants retired and rose at their usual time, and this waskept constant for all study nights and all preceding nights.Polysomnography involved a standard montage: four electro-encephalogram channels (C3/A2, C4/A1, O1/A2, O2/A1),two electro-oculogram channels, and a submentalis electro-myogram. Polysomnograms were staged in 30-s epochs usingthe Embla diagnostic software, Somnologica Studio. Thissoftware provides measures for all aspects of sleep architec-ture according to standard criteria. In addition, the polysomno-grams were edited by an experienced sleep physiologist blindto treatment status. The polysomnograms of two participantswere excluded due to technical difficulties. However, theirsubjective ratings were available and were included. Differ-ences between the pairs of sleep nights were assessed usingStudent’spairedt test (two-tailed).Agomelatine produced no change in any polysomno-graphic parameter including SWS (Table 1). Separate exam-ination of sequential cycles of SWS also failed to reveal anyeffect of agomelatine (data not shown). Following agomela-tine, participants rated their sleep quality as improved, butthey also experienced more nausea (Table 1).Our findings suggest that initiation of a standard clinicaldose of agomelatine does not cause functional blockade ofbrain 5-HT