GABAA receptor positive allosteric modulator

A class of drugs that enhance the activity of the GABA_A receptor

GABA_A Receptor Positive Allosteric Modulators

File:GABAA receptor structure.png

Diagram of the GABA_A receptor structure.

GABA_A receptor positive allosteric modulators are a class of drugs that enhance the activity of the [[GABA_A receptor]], a type of ligand-gated ion channel in the central nervous system. These modulators do not activate the receptor directly but increase the receptor's response to the neurotransmitter gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain.

Mechanism of Action

GABA_A receptors are pentameric structures composed of various subunits, which form a chloride ion channel. When GABA binds to these receptors, the channel opens, allowing chloride ions to enter the neuron, leading to hyperpolarization and decreased neuronal excitability. Positive allosteric modulators bind to sites distinct from the GABA binding site, enhancing the receptor's response to GABA.

Types of Modulators

There are several classes of GABA_A receptor positive allosteric modulators, including:

• Benzodiazepines: These are among the most well-known modulators, used for their anxiolytic, sedative, muscle relaxant, and anticonvulsant properties. Common benzodiazepines include diazepam, lorazepam, and alprazolam.

• Barbiturates: Although less commonly used today due to their side effect profile, barbiturates like phenobarbital and pentobarbital are effective modulators.

• Z-drugs: These include zolpidem, zaleplon, and eszopiclone, which are primarily used for the treatment of insomnia.

• Neuroactive steroids: Endogenous and synthetic steroids that modulate GABA_A receptors, such as allopregnanolone.

Clinical Uses

File:Diazepam-3D-balls.png

3D model of diazepam, a common benzodiazepine.

GABA_A receptor positive allosteric modulators are used in various clinical settings:

• Anxiety Disorders: Benzodiazepines are commonly prescribed for short-term relief of severe anxiety.

• Insomnia: Z-drugs and certain benzodiazepines are used to treat sleep disorders.

• Seizure Disorders: Both benzodiazepines and barbiturates are used as anticonvulsants.

• Muscle Spasms: Benzodiazepines can be used to relieve muscle spasms due to their muscle relaxant properties.

Side Effects and Risks

While effective, these modulators can have significant side effects, including:

• Sedation: Excessive drowsiness and impaired motor coordination.
• Dependence and Withdrawal: Long-term use can lead to physical dependence and withdrawal symptoms upon cessation.
• Cognitive Impairment: Memory and cognitive function can be affected, especially with prolonged use.

Related Pages

• [[GABA_A receptor]]
• Benzodiazepine
• Barbiturate
• Z-drug
• Neurotransmitter