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What is Gamma butyrolactones (GBL)?
This compound belongs to the class of organic compounds known as gamma butyrolactones. These are compounds containing a gamma butyrolactone moiety, which consists of an aliphatic five-member ring with four carbon atoms, one oxygen atom, and bears a ketone group on the carbon adjacent to the oxygen atom. Also One of the FURANS with a carbonyl thereby forming a cyclic lactone. Furthermore Gamma-Butyrolactone is an endogenous compound from gamma-aminobutyrate and is the precursor of gamma-hydroxybutyrate. Also it is also put in use as a pharmacological agent and solvent.
GBL is not active in its own right; its mechanism of action stems from its identity as a prodrug of GHB. It blocks dopamine release by blocking impulse flow in dopaminergic neurons. Pretreatment with γ-butyrolactone allows detection of autoreceptor-induced dopamine release. Also the hypnotic effect of GHB enhances in combination with alcohol. Furthermore a 2003 rat study shows that GBL in combination with ethanol shows a potential hypnotic effect, as the sleep-timing measure is longer than both of the individual components.
However GBL rapidly converts into GHB by paraoxonase (lactonase) enzymes, found in the blood. Animals which lack these enzymes exhibit no effect from GBL. Also GBL is more lipophilic (fat soluble) than GHB, is absorbes faster and has higher bioavailability. Also because of these pharmacokinetic differences, GBL tends to be more potent and faster-acting than GHB, but has a shorter duration. Whereas the related compound 1,4-butanediol (1,4-B) tends to be slightly less potent, slower to take effect but longer-acting than GHB.
Absorption, Distribution and Excretion
Gamma-Butyrolactone appears to be readily for absorbtion through guinea pig skin. In rat, at least 10% of the dose penetrates the skin. Also data describing the uptake of gamma-butyrolactone from the gastrointestinal or the respiratory system are not in a location in the literature. However biological degradation of gamma-butyrolactone in mammals is rapid. It hydrolyzes to gamma-hydroxybutyric acid in the blood and liver. In rats, gamma-hydroxybutyric acid excrets as CO2. Also gamma-Butyrolactone has a weak narcotic effect due to its fast metabolic conversion to gamma-hydroxybutyric acid, which has an effect on the central nervous system.
Gamma-Butyrolactone undergoes rapid and quantitative conversion by lactonases, yielding gamma-hydroxybutyric acid. Also Lactonases have been identified in human blood and in the blood and liver of rats, but not in the rat brain, spleen, kidney, heart, diaphragm, lung skeletal muscle or gastrointestinal tract. Furthermore the enzyme isolated from human plasma had a markedly higher activity than that isolated from rat liver microsomes. Moreover, conversion in human serum had a Km value of 2.7 x 10-2 M and thus was more efficient than in rat serum (Km value 1.6 x 10-2 M…). In vitro rat blood studies gave a half-life of less than one minute for the conversion of gamma-butyrolactone to gamma-hydroxybutyric acid.