beta(1)-adrenergic antagonists improve sleep and behavioural disturbances in a circadian disorder, Smith-Magenis syndrome

J Med Genet. 2001 Sep;38(9):586-90. doi: 10.1136/jmg.38.9.586.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acebutolol / pharmacology
  • Acebutolol / therapeutic use
  • Adolescent
  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Behavior / drug effects
  • Behavior / physiology
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 17 / genetics
  • Chronobiology Disorders / drug therapy*
  • Chronobiology Disorders / genetics
  • Chronobiology Disorders / physiopathology
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology
  • Cognition / drug effects
  • Female
  • Humans
  • Hyperkinesis / drug therapy
  • Hyperkinesis / genetics
  • Hyperkinesis / physiopathology
  • In Situ Hybridization, Fluorescence
  • Male
  • Melatonin / blood
  • Sleep / drug effects
  • Sleep / genetics
  • Sleep / physiology
  • Sleep Wake Disorders / drug therapy*
  • Sleep Wake Disorders / genetics
  • Sleep Wake Disorders / physiopathology
  • Syndrome
  • Wakefulness / drug effects
  • Wakefulness / genetics
  • Wakefulness / physiology

Substances

  • Adrenergic beta-Antagonists
  • Acebutolol
  • Melatonin