Detection of gamma-hydroxybutyrate in striatal microdialysates following peripheral 1,4-butanediol administration in rats.
The illicit use and abuse of 1,4-butanediol (1,4-BD) results from its presumed conversion to gamma-hydroxybutyrate (GHB) and subsequent pharmacological effects via action on GABA-B and GHB-specific receptors. Using in vivo microdialysis we measured the appearance of GHB in the striata of rats after peripheral 1,4-BD administration. We developed and utilized an HPLC-UV (215 nm) detection of GHB that yielded a limit of quantification (S/N=10) of 2.0 micro g/mL (40 ng/injection) and a limit of detection (S/N=3) of 0.75 micro g/mL (15 ng/injection). GHB appeared in the striatal microdialysates within 20 min after intraperitoneal (i.p.) administration of varying doses of 1,4-BD. GHB concentrations reached dose-dependent maxima 80-100 min post-1,4-BD administration, with peak values of 10.6+/-2.9, 25.3+/-3.4 and 48.1+/-7.1 micro g/mL (mean+/-S.E.M.), corresponding to 1,4-BD doses of 250, 500 and 750 mg/kg, respectively. The conversion of 1,4-BD to GHB was completely prevented by the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP), administered prior to 1,4-BD, as evidenced by the failure of GHB to appear in the striatal microdialysates. Sleep times in animals were similarly correlated with GHB concentrations in the microdialysates.
Kapadia
Roopa
R
Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USA.
Böhlke
Mark
M
Maher
Timothy J
TJ
D000759:Adjuvants, Anesthesia / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D000077604:Fomepizole; D013287:Illicit Drugs / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis / Q000379:methods*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects; D012978:Sodium Oxybate / Q000032:analysis / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet
D000759:Adjuvants, Anesthesia; D000931:Antidotes; D013287:Illicit Drugs; D011720:Pyrazoles; D012978:Sodium Oxybate; D000077604:Fomepizole