title: Gamma hydroxybutyrate is not a GABA agonist.
abstract: 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.
authors.affiliation: American Institute of Biotechnology, Department of Research and Development, Elk Grove Village, IL 60007, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Feigenbaum
authors.forename: S G
authors.initials: SG
authors.lastname: Howard
mesh_terms: D015107:4-Butyrolactone / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D003292:Convulsants / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D018755:GABA Agonists; D006801:Humans; D008322:Mammals / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced; D012978:Sodium Oxybate / Q000378:metabolism / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D015107:4-Butyrolactone; D003292:Convulsants; D018755:GABA Agonists; D010852:Picrotoxin; D018079:Receptors, GABA; D012978:Sodium Oxybate; D005680:gamma-Aminobutyric Acid