Aberrant mTOR signaling and disrupted autophagy: The missing link in potential vigabatrin-associated ocular toxicity?

Clin Pharmacol Ther. 2017 Apr;101(4):458-461. doi: 10.1002/cpt.581. Epub 2017 Feb 7.

Abstract

Vigabatrin (VGB; γ-vinylGABA) is a unique antiepileptic directly elevating CNS GABA via inactivation of the GABA metabolic enzyme GABA-transaminase. VGB is effective in treating infantile spasms, a rare seizure disorder associated with significant morbidity. The potential for unexplained bilateral constriction of the visual field associated with VGB intervention can severely limit its temporal utility. Removal of this potential adverse effect with adjuvant intervention(s) would represent a significant advance in epilepsy therapeutics.

MeSH terms

  • Anticonvulsants / adverse effects*
  • Autophagy / drug effects*
  • Evoked Potentials, Visual
  • Humans
  • Infant
  • Infant, Newborn
  • Signal Transduction
  • Spasms, Infantile
  • TOR Serine-Threonine Kinases / drug effects*
  • Vigabatrin / adverse effects*
  • Vision Disorders / chemically induced*
  • Vision Disorders / physiopathology
  • gamma-Aminobutyric Acid / biosynthesis

Substances

  • Anticonvulsants
  • gamma-Aminobutyric Acid
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Vigabatrin