SCH-50911
Encyclopedia
SCH-50911 is a selective GABAB
antagonist
developed by Schering-Plough Corporation. 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), only 2 out of 20 of the mice died (10%), compared to 100% lethality in the control group.
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 GABAB 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 delirium tremens
seen in human alcohol withdrawal, and can precipitate convulsions in GHB-dependent animals.
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.
GABA B receptor
GABAB receptors are metabotropic transmembrane receptors for gamma-aminobutyric acid that are linked via G-proteins to potassium channels...
antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
developed by Schering-Plough Corporation. Its main applications are in pharmacology research, but it has been found to quickly and effectively reverse the symptoms of GHB
Gamma-Hydroxybutyric acid
γ-Hydroxybutyric acid , also known as 4-hydroxybutanoic acid and sodium oxybate when used for medicinal purposes, is a naturally occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts. It is also categorized as an illegal...
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), only 2 out of 20 of the mice died (10%), compared to 100% lethality in the control group.
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 GABAB agonists such as Baclofen
Baclofen
Baclofen is a derivative of gamma-aminobutyric acid . It is primarily used to treat spasticity and is under investigation for the treatment of alcoholism....
. 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 delirium tremens
Delirium tremens
Delirium tremens is an acute episode of delirium that is usually caused by withdrawal from alcohol, first described in 1813...
seen in human alcohol withdrawal, and can precipitate convulsions in GHB-dependent animals.
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
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
would most likely be required to counteract the risk of life-threatening seizures. This is similar to the problems seen with opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
antagonists such as naloxone
Naloxone
Naloxone is an opioid antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug used to counter the effects of opiate overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory...
, which are useful antidotes to opiate overdose but may precipitate acute withdrawal syndrome in opiate-addicted individuals.