title: Lack of effects of GHB precursors GBL and 1,4-BD following i.c.v. administration in rats.
abstract: Gamma-hydroxybutyrate (GHB) is used therapeutically and recreationally worldwide. Since the scheduling of GHB by the USA and the United Nations in 2000-2001, the recreational use of GHB precursors has reportedly increased. The aim of this study was to examine if potency differences of GHB and GHB-like compounds are due to their blood-brain barrier permeability. The effects of peripheral and central administration of GHB, GHB precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), and the gamma-aminobutyric acid (GABA)(B) receptor agonist baclofen on schedule-controlled responding were examined in rats. GHB and baclofen were 276- and 253-fold more potent, respectively, after intracerebroventricular (i.c.v.) administration than after intraperitoneal (i.p.) administration, whereas GBL and 1,4-BD, up to a dose of 1780 microg were without effect after i.c.v. administration. These data suggest that GBL and 1,4-BD are not metabolically converted to GHB in the brain, that enhanced brain penetration cannot account for potency differences between compounds, and that baclofen, like GHB, can readily cross the blood-brain barrier.
authors.affiliation: The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive - MC7764, San Antonio, TX 78229, USA.
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: Carter
authors.forename: Wouter
authors.initials: W
authors.lastname: Koek
authors.forename: Charles P
authors.initials: CP
authors.lastname: France
mesh_terms: D015107:4-Butyrolactone / Q000008:administration & dosage* / Q000378:metabolism*; D018686:Anesthetics, Intravenous; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects*; D002072:Butylene Glycols / Q000008:administration & dosage* / Q000378:metabolism*; D018755:GABA Agonists / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012978:Sodium Oxybate / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D018686:Anesthetics, Intravenous; D002072:Butylene Glycols; D018755:GABA Agonists; D012978:Sodium Oxybate; C039681:1,4-butanediol; D001418:Baclofen; D015107:4-Butyrolactone