SCH-50911

SCH-50911 is a selective GABA_B antagonist.^[1] Its main applications are in pharmacology research, but it has been found to quickly and effectively reverse the symptoms of GHB overdose in mice. In one experiment, mice were given a lethal dose of GHB (7000mg/kg) followed by varying doses of SCH-50911. At the two higher doses of the antagonist (150mg/kg and 300mg/kg), 18 out of 20 of the mice survived (90%), compared to 100% lethality in the control group.^[2]

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SCH-50911 also acts as an anticonvulsant under normal conditions, and so counteracts both the depressant and pro-convulsant effects of GHB overdose. This pharmacological profile makes SCH-50911 a promising candidate as a GHB antidote for human use, and might also make it useful for treating overdoses of other GABA_B agonists such as Baclofen. SCH-50911 has never been tested for this purpose in humans and there are no plans at this stage to develop it for these applications. However SCH-50911 induces acute withdrawal syndrome in GHB-dependent rats, similar to the delerium tremens seen in human alcohol withdrawal, and can precipitate convulsions in GHB-dependent animals.^[3]

This means that while SCH-50911 is likely to be a useful antidote for GHB overdose in non-addicted individuals, its use in people who are dependent on GHB or its analogues could be potentially dangerous as it might precipitate acute withdrawal symptoms, and additional anticonvulsants such as diazepam would most likely be required to counteract the risk of life-threatening seizures. This is similar to the problems seen with opioid antagonists such as naloxone, which are useful antidotes to opiate overdose but may precipitate acute withdrawal syndrome in opiate-addicted individuals.

References

1. ^ Blythin DJ, Kuo SC, Shue HJ, McPhail AT, Chapman RW, Kreutner W, Rizzo C, She HS, West R. Substituted morpholine-2S-acetic acid derivatives: SCH 50911 and Related Compounds as Novel GABA_B Antagonists. Bioorganic and Medicinal Chemistry Letters. 1996 Jul 9; 6(13): 1529-1534.
2. ^ Carai MA, Colombo G, Gessa GL. Resuscitative effect of a gamma-aminobutyric acid B receptor antagonist on gamma-hydroxybutyric acid mortality in mice. Annals of Emergency Medicine 2005 Jun;45(6):614-9.
3. ^ Quang LS, Colombo G, Lobina C, Maccioni P, Orru A, Gessa GL, Maher TJ, Carai MA. Evaluation for the withdrawal syndrome from gamma-hydroxybutyric acid (GHB), gamma-butyrolactone (GBL), and 1,4-butanediol (1,4-BD) in different rat lines. Annals of the New York Academy of Science. 2006 Aug;1074:545-58.