Gamma hydroxybutyrate is not a GABA agonist

Prog Neurobiol. 1996 Sep;50(1):1-7. doi: 10.1016/0301-0082(96)00029-9.


Gamma hydroxybutyrate (GHB) is primarily known and used as a relatively specific inhibitor of central DA release. However, it is also widely assumed to be an agonist or prodrug of gamma-aminobutyric acid (GABA) and its central activity has been attributed to an action exerted at GABA receptors. Nevertheless, there is compelling evidence that: (1) GHB formation may occur independently of GABA; (2) GHB is behaviorally, biochemically and physiologically distinct from GABA in many ways, and does not consistently effect GABAA or GABAB agonist induced responses; (3) GHB has little effect on either GABAA or GABAB receptors at less than millimolar concentrations. Consequently, GHB does not appear to be either a GABA prodrug or a GABA agonist. However, the GHB metabolite gamma butyrolactone (GBL) may possess some limited GABA agonist activity.

Publication types

  • Review

MeSH terms

  • 4-Butyrolactone / metabolism
  • 4-Butyrolactone / pharmacology
  • Animals
  • Central Nervous System / drug effects
  • Convulsants / pharmacology
  • Electroencephalography / drug effects
  • GABA Agonists*
  • Humans
  • Mammals / metabolism
  • Muscle Contraction / drug effects
  • Picrotoxin / pharmacology
  • Rabbits
  • Rats
  • Receptors, GABA / drug effects
  • Receptors, GABA / metabolism
  • Respiration / drug effects
  • Seizures / chemically induced
  • Sodium Oxybate / metabolism
  • Sodium Oxybate / pharmacology*
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacokinetics


  • Convulsants
  • GABA Agonists
  • Receptors, GABA
  • Picrotoxin
  • gamma-Aminobutyric Acid
  • Sodium Oxybate
  • 4-Butyrolactone