title: beta(1)-adrenergic antagonists improve sleep and behavioural disturbances in a circadian disorder, Smith-Magenis syndrome.
abstract: Smith-Magenis syndrome (SMS) is a clinically recognisable contiguous gene syndrome ascribed to interstitial deletions of chromosome 17p11.2. Patients have a phase shift of their circadian rhythm of melatonin with a paradoxical diurnal secretion of the hormone. Serum melatonin levels and day-night behaviour were studied in nine SMS children (aged 4 to 17 years) given acebutolol, a selective beta(1)-adrenergic antagonist (10 mg/kg early in the morning). Cardiac examination, serum melatonin, motor activity recordings, and sleep diaries were monitored before and after drug administration. The present study shows that a single morning dose of acebutolol suppressed the inappropriate secretion of melatonin in SMS. A significant improvement of inappropriate behaviour with increased concentration, delayed sleep onset, increased hours of sleep, and delayed waking were also noted. These results suggest that beta(1)-adrenergic antagonists help to manage hyperactivity, enhance cognitive performance, and reduce sleep disorders in SMS.
authors.affiliation: Department of Genetics and Unit INSERM 393, Hôpital Necker Enfants-Malades, 149 rue de Sevres, 75743 Paris Cedex 15, France.
authors.forename: H
authors.initials: H
authors.lastname: De Leersnyder
authors.forename: M C
authors.initials: MC
authors.lastname: de Blois
authors.forename: M
authors.initials: M
authors.lastname: Vekemans
authors.forename: D
authors.initials: D
authors.lastname: Sidi
authors.forename: E
authors.initials: E
authors.lastname: Villain
authors.forename: C
authors.initials: C
authors.lastname: Kindermans
authors.forename: A
authors.initials: A
authors.lastname: Munnich
mesh_terms: D000070:Acebutolol / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D001519:Behavior / Q000187:drug effects / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D021081:Chronobiology Disorders / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects; D005260:Female; D006801:Humans; D006948:Hyperkinesis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008550:Melatonin / Q000097:blood; D012890:Sleep / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D012893:Sleep Wake Disorders / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D013577:Syndrome; D014851:Wakefulness / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D000070:Acebutolol; D008550:Melatonin