GBL is rapidly and irreversibly hydrolysed into GHB by peripheral gamma-lactonase. GBL is more rapidly absorbed and has greater
bioavailability than GHB on an equimolar basis. In spite of the rapid hydrolysis of the lactone in blood, the distributive pattern of GBL may
be different from that of GHB. This can be one reason why GBL gives more prolonged hypnotic effects than GHB.
According to Roth and Giarman GBL is hydrolysed in blood and liver.
References:
Lettieri J, Fung H-L "Improved pharmacological activity via
pro-drug modification: comparative pharmacokinetics of sodium
gamma-hydroxybutyrate and gamma-butyrolactone"
Research Communications in Chemical Pathology and Pharmacology
1978, 22(1)107-118
Bernasconi R, Mathivet P, Bischoff S, Marescaux C
"Gamma-hydroxybutyric acid: an endogenous neuromodulator with
abuse potential?" Trends in Pharmacological Sciences 1999 vol.20, 135-141
Roth RH, Giarman NJ, "Gamma-butyrolactone and
gamma-hydroxybutyric acid. I. Distribution and metabolism.
Biochemical Pharmacology, 1966, vol. 15, pp. 1333-1348
...
Found this from Toxline:
1,4-Butandiol
Authors:
Anonymous
Source: TA:Toxikologische Bewertung. Heidelberg, Berufsgenossenschaft der chemischen Industrie PG:29 p YR:1993 IP:
VI:99
Abstract:
1,4-Butanediol is metabolized to 4-hydroxybutyric acid, CO2, y-butyrolactone and succinic acid in various species of animal (e.g. mouse, rat, monkey) and in man. Succinic acid enters the citric acid cycle. The ultimate metabolite of 1,4-butanediol is CO2, which is predominantly eliminated via the lungs. The pharmacological effects in animals (sedation and narcosis) are probably chiefly caused by the metabolite 4-hydroxybutyric acid. According to the available acute toxicity studies, 1,4-butanediol is moderately toxic in animals (oral LD50 rat, between 1350 and 1780 mg/kg body weight; 4-hour LC50 values rat, > 5.1 and > 15 mg/l air). In rats and mice, intraperitoneal administration of 1,4-butanediol has marked narcotic and hypothermic effects. The threshold dose for the narcotic effect in the rat after intraperitoneal administration lies between 100 and 250 mg/kg body weight. Local application of neat 1,4-butanediol to rabbits causes mild skin irritation. The irritant effect on the eye is also mild. No characteristic signs of toxicity occur on oral administration of 0.25 or 3 mg/kg body weight/day to rats for 6 months. A dose of 30 mg/kg causes impairment of conditioned reflexes, as well as reduced cholinesterase and increased transaminase activities, reduced SH-group levels and an altered protein profile in the serum. Histologically, effects are seen in the brain, and fatty degeneration and sclerosis are found in the liver. In inhalation studies, slight histological changes are found in the lungs of rats after subacute exposure (0.003 to 0.005 mg/l for 2 hours daily for 30 days) and after subchronic exposure (0.3 to 0.5 mg/l for 4 hours daily or 1.5 to 2 mg/l for 2 hours daily, both for 4 months). A no effect level has been established. However, these findings appear questionable, as no such effects have been seen in subsequent 2-week subacute inhalation studies with exposure for 6 hours/day at concentrations that have been up to 1000-fold higher. The no effect level in these studies has been 1.1 mg/l. 1,4-Butanediol has shown no mutagenic activity in the Salmonella/microsome test or in Drosophila melanogaster. In man, sleep is induced by intravenous administration of 30 mg/kg body weight or by infusion of 15 to 22 mg/kg/hour for about 38 to 68 hours (initial dose 30 mg/kg body weight i.v.). Undesirable side-effects which may occur include restlessness and clonic spasms of the muscle of the extremities. Rectal administration of 15 or 30 g 1,4-butanediol (214 and 429 mg/kg body weight, respectively, at an assumed body weight of 70 kg) have led to coma and deep unconsciousness. 2 out of 7 patients have died within 72 hours, while the remainder has recovered. Based on the subchronic inhalation studies, a MAK value of 500 mg/m3 has been proposed for 1,4-butanediol in the former Soviet Union.
...
Templar, the effects of GHB on dopaminergic transmission are time and concentration dependent, thus it's very hard to say what are the consequences of concurrent administration of GHB and MDMA. There is one study, where injection of gamma-butyrolactone (400 mg kg-1, i.p.) 5 min before and 55 min after MDMA provided substantial protection against neurotoxicity.
The authors of the study I was refering to concluded that GBL most likely inhibited dopamine function, although it rised striatal dopamine levels (it has very time-dependent effects). My suggestion is that the observed neuroprotection was mainly due to hypothermia produced by GBL. In the study I was refering to, they didn't measure core temperature of rats. GHB/GBL has been observed to produce hypothermia in
experimental animals and decreased core temperature is known to attenuate the MDMA-induced neurotoxicity.
...
Two recent studies give some nice theories how GHB could help to methamphetamine comedown.
Barbaccia ML, Colombo G, Affricano D, Carai MA, Vacca G, Melis S, Purdy RH, Gessa GL.
GABA(B) receptor-mediated increase of neurosteroids by gamma-hydroxybutyric acid.
Neuropharmacology. 2002 May;42(6):782-91.
Gobaille S, Schleef C, Hechler V, Viry S, Aunis D, Maitre M.
Gamma-hydroxybutyrate increases tryptophan availability and potentiates serotonin turnover in rat brain.
Life Sci. 2002 Mar 22;70(18):2101-12.
