beta(1)-adrenergic antagonists improve sleep and behavioural disturbances in a circadian disorder, Smith-Magenis syndrome.
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.
De Leersnyder
H
H
Department of Genetics and Unit INSERM 393, Hôpital Necker Enfants-Malades, 149 rue de Sevres, 75743 Paris Cedex 15, France.
de Blois
M C
MC
Vekemans
M
M
Sidi
D
D
Villain
E
E
Kindermans
C
C
Munnich
A
A
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
D000319:Adrenergic beta-Antagonists; D000070:Acebutolol; D008550:Melatonin