QH-II-66
Encyclopedia
QH-II-66 is a sedative
drug which is a benzodiazepine
derivative. It produces some of the same effects as other benzodiazepines, but is much more selective than most other drugs of this class and so produces somewhat less sedation and ataxia
than other related drugs such as diazepam
and triazolam
, although it still retains anticonvulsant
effects.
QH-ii-066 is a highly subtype-selective GABAA agonist
which was designed to bind selectively to the α5 subtype
of GABAA receptors.
The α5 subtype (and to a lesser extent the α1 subtype) of GABAA are two of the most important targets in the brain that produce the effects of alcohol
, and so one of the purposes for which QH-ii-066 was developed was to reproduce the GABAergic
effects of alcohol separately from its other actions.
QH-ii-066 replicates some of the effects of alcohol, such as sedation and ataxia, but does not increase appetite, as this effect seems to be produced by the α1 subtype of GABAA rather than α5. It is also interesting to note that the inverse agonist
Ro15-4513
, which blocks the α4 subtype of GABAA, reverses the effects of alcohol, suggesting that this subtype is also important in producing the subjective effects of alcohol intoxication.
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
drug which is a benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
derivative. It produces some of the same effects as other benzodiazepines, but is much more selective than most other drugs of this class and so produces somewhat less sedation and ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
than other related drugs 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,...
and triazolam
Triazolam
Triazolam is a benzodiazepine drug. It possesses pharmacological properties similar to that of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia...
, although it still retains anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
effects.
QH-ii-066 is a highly subtype-selective GABAA agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
which was designed to bind selectively to the α5 subtype
GABRA5
Gamma-aminobutyric acid A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the GABRA5 gene.-Function:...
of GABAA receptors.
The α5 subtype (and to a lesser extent the α1 subtype) of GABAA are two of the most important targets in the brain that produce the effects of alcohol
Alcoholic beverage
An alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
, and so one of the purposes for which QH-ii-066 was developed was to reproduce the GABAergic
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
effects of alcohol separately from its other actions.
QH-ii-066 replicates some of the effects of alcohol, such as sedation and ataxia, but does not increase appetite, as this effect seems to be produced by the α1 subtype of GABAA rather than α5. It is also interesting to note that the inverse agonist
Inverse agonist
In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist....
Ro15-4513
Ro15-4513
Ro15-4513 is a weak partial inverse agonist of the benzodiazepine class of drugs, developed by Hoffmann–La Roche in 1984, and is structurally related to the benzodiazepine antidote flumazenil.-Original development as alcohol antidote:...
, which blocks the α4 subtype of GABAA, reverses the effects of alcohol, suggesting that this subtype is also important in producing the subjective effects of alcohol intoxication.