Chemical structure of GHBGamma-hydroxybutyrate powder
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Gamma-hydroxybutyrate (4-hydroxybutanoic acid, C4H8O3) is both a drug and a naturally occurring compound found in the central nervous system as well as in other organs as liver, kidneys, heart and bones. GHB is structurally similar to the ketone body beta-hydroxybutyrate. As a drug it is used most commonly in the form of a chemical salt (Na-GHB or K-GHB). The sodium salt is commercially known as sodium oxybate. more...




The precise function of GHB in body is not clear. It is an immediate precursor to GABA, a neurotransmitter which regulates awakeness, physical activity and sleep. As GABA cannot cross blood-brain barrier, GHB obtained from food may be used for converting to GABA. GHB prevents cells from oxygen starvation, which might explain presence of the compound in vital organs. GHB was also found to have neuroprotective capabilities.


It has been used as a general anesthetic, and a hypnotic in the treatment of insomnia. GHB has also been used to treat clinical depression, and improve athletic performance. In the United States, the Food and Drug Administration permits the use of GHB under the trade name Xyrem to reduce the number of cataplexy attacks in patients with narcolepsy.


GHB is an intoxicant. It may be known as G, Liquid X, Liquid E. It is less commonly known as GBH, Gamma-oh, Georgia Homeboy, Blue Verve, Gamma-G, Qi, scoop, goop, Grievous Bodily Harm, or Get Hospitalised Bitch.

Its potential for use as a date rape drug in the 1990s led to it being placed in the US on Schedule I of the Controlled Substances Act in March, 2000. On March 20, 2001, the Commission on Narcotic Drugs placed GHB in Schedule IV of the 1971 Convention on Psychotropic Substances. In the UK it was made a class C drug in June 2003.

The sodium salt of GHB has a thin, very salty, chemical taste. At low doses, GHB can cause a state of euphoria, increased sociality and intoxication. This kind of use is particularly common at rave parties. At higher doses, GHB may induce nausea, dizziness, drowsiness, visual disturbances, depressed breathing, amnesia and unconsciousness. The effects of GHB can last from 1.5 to 3 hours.

Some chemicals convert to GHB in the stomach and blood. GBL, or gamma-butyrolactone, is one such precursor. It is 1,6 times more potent than GHB, so 1ml of GBL is equivalent to 0,4g of GHB. GBL has also a shorter onset and is longer acting than GHB. GBL has an extremely bad taste and is also known to irritate innards and skin.

Other precursors include 1,4-butanediol. There may be additional toxicity concerns with these precursors.

Mode of action

The action of GHB has yet to be fully elucidated. GHB clearly has at least two sites of action, stimulating the newly characterized and aptly named "GHB receptor" as well as the GABAB. GHB, if it is indeed a neurotransmitter, will only reach concentrations high enough to act at the GHB receptor, as it only has weak affinity fo the GABAB. However, during recreational usage, GHB can reach very high concentrations in the brain, relative to basal levels, and can act at the GABAB receptor . GHBs action at the GABAB is probably responsible for its sedative effects. GHB-mediated GABAB receptor stimulation inhibits dopamine release as well as causes the release of natural sedative neurosteroids (like all other GABAB agonists e.g. Baclofen). In animals GHBs sedative effects can be stopped by GABAB antagonists (blockers).


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Orphan Medical Issues Xyrem Prescriptions Update
From Business Wire, 5/23/05

MINNEAPOLIS -- ORPHAN MEDICAL, INC. (Nasdaq:ORPH) announced that the total number of Xyrem(R) (sodium oxybate) oral solution prescriptions filled in the six-week period ended May 15, 2005, was 5,268, up from both 2,962 for the same prior-year period and 5,010 for the six-week period ended March 31, 2005. In addition, the number of prescribers increased to nearly 2,450 from approximately 1,150 a year ago.

Xyrem is currently marketed as the first and only approved treatment for cataplexy, a sudden loss of muscle tone, a debilitating symptom of narcolepsy. An sNDA for Xyrem is under review by the FDA and, if approved, is expected to expand the Xyrem label to encompass the other primary symptoms of narcolepsy, specifically the reduction of excessive daytime sleepiness (EDS) and improvement in fragmented nighttime sleep.

The Company reiterated that the data from the clinical trial designed to evaluate Xyrem in the treatment of fibromyalgia syndrome is expected to be available in the second half of 2005.

About Narcolepsy

Narcolepsy is a chronic, debilitating neurological disease. Cataplexy, a sudden loss of muscle tone, is usually triggered by strong emotions such as laughter, anger or surprise. As such, patients often selectively isolate themselves from interaction with others resulting in a worsening effect on a patient's quality of life. Narcolepsy afflicts approximately 100,000 to 140,000 Americans with about 50,000 to 75,000 patients receiving some form of treatment for their symptoms. An estimated 60 to 90 percent of those with narcolepsy suffer from cataplexy. All patients with narcolepsy suffer from EDS.

About Fibromyalgia

Fibromyalgia is a chronic condition that is estimated to affect over four million individuals in the United States and represents a market opportunity in excess of $1 billion per year. The disease is characterized by widespread muscle pain and stiffness and affects women three times more often than men. Other symptoms include persistent fatigue, headaches, cognitive or memory impairment, morning stiffness and non-restorative sleep.

About Orphan Medical

Orphan Medical acquires, develops, and markets pharmaceuticals of high medical value for inadequately treated and uncommon central nervous system diseases treated by specialist physicians. The Company's lead product is Xyrem, which is the first and only approved treatment for cataplexy associated with narcolepsy. Xyrem is being assessed as a treatment for the full range of narcolepsy symptoms including excessive daytime sleepiness. The Company is also conducting a trial to evaluate Xyrem as a treatment for symptoms of fibromyalgia syndrome. Orphan Medical's Internet Web site address is

Notice to Investors

The pending merger with Jazz Pharmaceuticals has not been consummated. Orphan Medical has filed a proxy statement with the Securities and Exchange Commission (SEC). The proxy statement contains important information that should be read carefully before any decision is made with respect to the merger. Investors may obtain a free copy of the proxy statement (and all other offer documents filed with the SEC) on the SEC's Web site ( and on Orphan Medical's Web site (

The information in this press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward-looking statements by terminology such as "expects," "anticipates," "intends," "may," "should," "plans," "believes," "seeks," "estimates," "could," "would" or the negative of such terms or other comparable terminology. Such forward-looking statements are based upon current expectations and beliefs and involve numerous risks and uncertainties, both known and unknown, that could cause actual events or results to differ materially from these forward-looking statements. The following factors, among others, could cause actual results to differ materially from these assumptions and expectations: the ability to obtain Orphan Medical stockholders' approval of the transaction; the ability of Jazz Pharmaceuticals to obtain senior debt financing; the ability to satisfy other closing conditions; disruption from the transaction making it more difficult to maintain relationships with customers, employees or suppliers; and the risk of new and changing regulation in the U.S. and internationally. Additional factors that could cause Orphan Medical's results to differ materially from those described in the forward-looking statements can be found in Orphan Medical's most recent Form 10-Q or Form 10-K filed with the SEC. (These documents can be accessed through the Orphan Medical Web site at ( All forward-looking statements are qualified by, and should be considered in conjunction with, such cautionary statements.

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