摘要：

Gamma-hydroxybutyrate penetrates freely into the brain when administered intravenously or intraperitoneally. This is a unique situation for a molecule with signalling properties in the brain. Thus, the γ-hydroxybutyrate concentration in brain easily can be increased more than 100 times. Under these conditions, γ-hydroxybutyrate receptors are saturated and probably desensitized and down-regulated. It is unlikely that GABA B receptors could be stimulated directly by GHB. Most probably, GABA is released in part under the control of GHB receptors in specific pathways expressing GABA B receptors. Alternatively, GABA B receptors might be specifically stimulated by the GABA formed via the metabolism of γ-hydroxybutyrate in brain. In animals and man, these GHBergic and GABAergic potentiations induce dopaminergic hyperactivity (which follows the first phase of dopaminergic terminal hyperpolarization), a strong sedation with anaesthesia and some EEG changes with epileptic spikes. It is presumed that, under pathological conditions (hepatic failure, alcoholic intoxication, succinic semialdehyde dehydrogenase defects), the rate of GHB synthesis or degradation in the peripheral organ is modified and induces increased GHB levels which could interfere with the normal brain mechanisms. This pathological status could benefit from treatments with γ-hydroxybutyric and/or GABA B receptors antagonists. Nevertheless, the regulating properties of the endogenous γ-hydroxybutyrate system on the dopaminergic pathways are a cause for the recent interest in synthetic ligands acting specifically at γ-hydroxybutyrate receptors and devoid of any role as metabolic precursor of GABA in brain. 1997 Elsevier Science Ltd. All Rights Reserved.

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