title: Comparative study of equimolar doses of gamma-hydroxybutyrate (GHB), 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) on catalepsy after acute and chronic administration.
abstract: Gamma-hydroxybutyrate (GHB), and its precursors 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) are known drugs of abuse. The ability of acute and chronic administration of equimolar doses of GHB (200mg/kg), 1,4-BD (174mg/kg) and GBL (166mg/kg) to produce catalepsy in male Swiss Webster mice was examined. GHB, 1,4-BD, GBL produced catalepsy when injected acutely. Drug treatment was then continued for 14days. Tolerance development was determined on days 6, 14, and challenged with a higher dose on day 15 in those chronically pretreated mice, and compared with naïve mice. Chronic GHB produced tolerance to catalepsy, as evidenced from area under the curve (AUC) of catalepsy versus time (min-sec) on days 6 (678±254), 14 (272±247), which were less than those on day 1 (1923±269). However, less tolerance was seen from GBL or 1,4-BD, as AUCs on days 6 and 14 were not significantly lower than that of day 1. In conclusion, although equimolar doses were used, expecting similar levels of GHB in the body, 1,4-BD and GBL shared only some of the in vivo effects of GHB. The rate of metabolic conversion of 1,4-BD and GBL into GHB might be responsible for the differences in the tolerance development to these drugs.
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Pasarapa
authors.initials: P
authors.lastname: Towiwat
authors.forename: Siripan
authors.initials: S
authors.lastname: Phattanarudee
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Maher
mesh_terms: D015107:4-Butyrolactone / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D019540:Area Under Curve; D002072:Butylene Glycols / Q000008:administration & dosage* / Q000633:toxicity; D002375:Catalepsy / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D012978:Sodium Oxybate / Q000008:administration & dosage* / Q000633:toxicity; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
chemical_list: D002072:Butylene Glycols; D012978:Sodium Oxybate; C039681:1,4-butanediol; D015107:4-Butyrolactone