Gaboxadol
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Gaboxadol
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| Systematic (IUPAC) name | |
| 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one | |
| Identifiers | |
| CAS number | |
| ATC code | ? |
| PubChem | |
| Chemical data | |
| Formula | C6H8N2O2 |
| Mol. mass | 140.14 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
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| Legal status | |
| Routes | ? |
Gaboxadol was an experimental sleeping pill developed by Lundbeck and Merck. In March 2007, work was cancelled on the drug because of safety concerns. It acts on the GABA system, but in a very different way than benzodiazepines and 'z-drugs' (zolpidem, zaleplon, and zopiclone). Lundbeck states that gaboxadol also increases deep sleep (stage 4).
[edit] Mode of action
From Lundbeck site:
Gaboxadol is a direct-acting GABA-A receptor agonist with the chemical name 7-tetra hydroisoxazolo[5, 4-c]pyridin-3-ol (THIP).
Gaboxadol has a mode of action different from that of benzodiazepine receptor ligands. Thus, gaboxadol interacts directly with the GABA receptor site and activates GABA receptor populations, which are not modulated by benzodiazepines.
It has been suggested that the influence of direct-acting GABA-A agonists on NREM and REM sleep mimic the effect of a physiological increase in sleep need, suggesting GABA-A receptors may be involved in the homeostatic regulation of sleep. The effect of the direct acting GABA-A receptor agonist gaboxadol on sleep has been investigated in rats and humans. Gaboxadol increase the proportion of non-REM sleep in particular the slow wave sleep (deep sleep) without affecting the REM sleep. In details gaboxadol: increase the time spent in NREM sleep increase NREM sleep continuity enhance delta activity (deep sleep) within NREM sleep does not suppress REM sleep
Newer hypnotics like the indirect-acting positive GABA-A receptor benzodiazepine site modulators zolpidem, zopiclone and zaleplon, also increase the non-REM sleep, but in contrast to gaboxadol, reduce the slow wave sleep and REM sleep. The functional consequence of this altered sleep is impaired next-day performance and a sensation of fatigue, despite a full night’s sleep. In contrast, in human explorative studies, gaboxadol significantly improved the subjective sleep quality. These observations can be interpreted as if indirect acting GABA-A receptor modulators as the benzodiazepine like drugs produce sleep of a subjective poorer quality, whereas gaboxadol apparently enhance the quality of sleep.
[edit] Pipeline
In March, 2007, Merck and H. Lundbeck cancelled work on the drug, citing safety concerns and the failure of an efficacy trial [1].
