Behavioral effects and pharmacokinetics of gamma-hydroxybutyrate (GHB) precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons.
BACKGROUND
Gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are prodrugs for gamma-hydroxybutyrate (GHB). Like GHB, GBL and 1,4-BD are drugs of abuse, but their behavioral effects may differ from GHB under some conditions.


OBJECTIVE
The first study compared the behavioral effects of GBL (32-240 mg/kg) and 1,4-BD (32-240 mg/kg) with each other and to effects previously reported for GHB (32-420 mg/kg). A second study determined GHB pharmacokinetics following intragastric administration of GHB, GBL, and 1,4-BD.


METHODS
Operant responding for food, observed behavioral effects, and a fine-motor task occurred at multiple time intervals after administration of drug or vehicle. In a separate pharmacokinetics study, blood samples were collected across multiple time points after administration of GHB, GBL, and 1,4-BD.


RESULTS
Like GHB, GBL, and 1,4-BD impaired performance on the fine-motor task, but the onset of motor impairment differed across drugs. GBL and 1,4-BD dose dependently decreased the number of food pellets earned, but at lower doses than previously observed for GHB. Similar to GHB, both GBL and 1,4-BD produced sedation, muscle relaxation, gastrointestinal symptoms, and tremors/jerks. Administration of GBL and 1,4-BD produced higher maximum concentrations of GHB with shorter times to maximum concentrations of GHB in plasma when compared to GHB administration.


CONCLUSIONS
GBL and 1,4-BD produced behavioral effects similar to those previously reported with GHB and the time course of effects were related to blood levels of GHB. Given their higher potency and faster onset of effects, the abuse liability of GBL and 1,4-BD may be greater than GHB.
Goodwin
A K
AK
Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA. Goodwin@jhu.edu
Brown
P R
PR
Jansen
E E W
EE
Jakobs
C
C
Gibson
K M
KM
Weerts
E M
EM
D015107:4-Butyrolactone / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal / Q000187:drug effects*; D002072:Butylene Glycols / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005502:Food; D018757:GABA Modulators / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D010215:Papio; D011355:Prodrugs / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012201:Reward; D012978:Sodium Oxybate / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019966:Substance-Related Disorders / Q000523:psychology
D002072:Butylene Glycols; D018757:GABA Modulators; D011355:Prodrugs; D012978:Sodium Oxybate; C039681:1,4-butanediol; D015107:4-Butyrolactone