GHB receptor

In 1963, GHB was found to occur naturally in many mammalian cells, including those in the brain. Since that time, it has been purported to act as a neurotransmitter. GHB is both a precursor and metabolite of GABA, although it does not act directly on GABA receptor sites. Recently, a putative GHB receptor has been cloned. This means it may be possible that... 

The mechanism by which GHB affects dopamine in the central nervous system is unclear. Scientists believe, however, that GHB binds to a possible, yet thus far unidentified, GHB receptor in the brain or to a GABA receptor. It is also possible that GHB is metabolized by the liver and converted to GABA (although this seems unlikely), or that GHB administration... 

Gamma-hydroxybutyrate (y-hydroxybutyrate/GHB) is a naturally occurring metabolite of y-aminobutyric acid (GABA) and like GABA, it may possess CNS neuroinhibitory activity via specific GHB receptors. 

Furthermore, GHB can be further metabolized by p-oxidation to trans-4-hydroxycrotonic acid, which aisc can bind to the GHB receptor. Body builders use these compounds as well in an attempt to enhance the release of growth hormone. Usually, however, chronic abuse leads to tolerance, with a need to increase dcsing and a prcpensity to produce physical dependence (43). A sericus and difficult-to-treat withdrawal syndrcme frcm GHB abuse has been dccumented. 

Jensen, K. and Mody, I. (2001) GHB depresses fast excitatory and inhibitory synaptic transmission via GABAb receptors in mouse neocortical neurons. Cereb. Cortex 11,424 129. 

Snead, O. C., 3rd. (1996) Relation of the [3H]gamma-hydroxybutyric acid (GHB) binding site to the gamma-aminobutyric acidB (GABAb) receptor in rat brain. Biochem. Pharmacol. 52,1235-1243. 

Other drugs, like GHB and Rohypnol , can interact directly with the neurotransmitter receptors to either enhance or block the effects of the brain s own neurotransmitters. Still other drugs can alter the metabolic breakdown or clearance of certain neurotransmitters after they are released from the synaptic terminal, thereby altering how long the neurotransmitter affects the activity of other nearby neurons. 

Neuropharmacologic classification of addictive drugs by primary target (see text and Table 32-1). DA, dopamine GABA, 7-aminobutyric acid GHB, 7-hydroxybutyric acid GPCRs, G protein-coupled receptors THC, A9-tetrahydrocannabinol. 

It should be noted that in addition to the GABA(A)-R benzodiazepine-binding sites or central benzodiazepine Rs (CBZ-Rs) there are peripheral benzodiazepine Rs (PBZ-Rs) associated with the outer membrane of mitochondria in glial cells and cells of peripheral tissue and which are involved in cholesterol transport and hence in regulation of steroid hormone synthesis. The GABA(B)-Rs are metabotropic and coupled via heterotrimeric G proteins to Ca2+ and K+ channels (Chapter 5). The psychotropic GABA breakdown product y-hydroxybutyrate (GHB) also acts via heterodimeric G protein-linked receptors (see Chapter 5). 

GH, growth hormone GHB, y-hydroxybutyrate GHB-R, y-hydroxybutyrate receptor GH-RIF, growth hormone-release inhibiting factor, somatostatin... 

S. Gobaille, D. Aunis, and M. Maitre. Cloning and Characterization of a Rat Brain Receptor that Binds the Endogenous Neuromodulator Gamma-hydroxybutyrate (GHB). FASEB Journal 17 (12) (2003) 1691-1693. 

Fig. 15.12. The Biotransformation of 1,4-butanediol (BD) and y-butyrolactone (GBL) and the receptor sites for their metabolites, y-hydroxybutyrate (GHB), GABA, and trans-4-hydroxycrotonic acid (T-HCA).

Andrianmampandry C, Taieb O, Viry S, et ai. Cioning and characterization of a rat brain receptor that binds the endogenous neuromoduiator y-hydroxybutyrate (GHB). FASEB J 2003 17 1691-1693. 

GABA-A receptor thereby enhancing the action of GABA. Sodium oxybate is the sodium salt of Y-hydrox)rbutyrat commonly referred to as GHB. This dmg has a very specific indication which is the treatment of cataplexy in narcolepsy. Narcolepsy is a chronic sleep disorder and the narcoleptic patient will often present as having severe insomnia. Cataplexy is a sudden loss of muscle tone and strength, usually caused by an extreme emotional stimulus. This occurs regularly (approximately 75% of cases) in patients with narcolepsy. Treatment with sodium oxybate is reported to improve the symptoms of narcolepsy and also to reduce the number of occurrences of cataplexy. 

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