What medications work via GABA-A versus GABA-B receptors?

From the Guidelines

Medications that work via GABA-A receptors include benzodiazepines, barbiturates, and non-benzodiazepine hypnotics, whereas medications targeting GABA-B receptors primarily include baclofen and GHB. According to the most recent evidence 1, benzodiazepines such as clonazepam promote GABAergic inhibition by increasing the frequency of chloride channel opening, which is a characteristic of GABA-A receptor activation.

GABA-A Receptor Medications

Some key medications that work via GABA-A receptors include:

• Benzodiazepines (e.g., diazepam, lorazepam, alprazolam, and clonazepam) 1
• Barbiturates (e.g., phenobarbital and butalbital) 1
• Non-benzodiazepine hypnotics (e.g., zolpidem, zaleplon, and eszopiclone)

GABA-B Receptor Medications

In contrast, medications that target GABA-B receptors include:

• Baclofen, used as a muscle relaxant for conditions like spasticity
• GHB (gamma-hydroxybutyrate), which has limited medical use due to abuse potential, primarily for conditions like narcolepsy

The distinction between these receptor targets explains their different therapeutic applications: GABA-A medications are commonly used for anxiety, insomnia, and seizures, while GABA-B medications like baclofen are primarily used for muscle spasticity. It's essential to consider the specific clinical context and the most recent evidence when selecting medications that target GABA receptors, as their effects can significantly impact patient outcomes in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

Benzodiazepines interact at GABA A sites and opioids interact primarily at mu receptors Benzodiazepines, including lorazepam, produce increased CNS-depressant effects when administered with other CNS depressants

The medications that work via GABA-A receptors are:

• Diazepam 2
• Lorazepam 3

There is no information in the provided drug labels about medications that work via GABA-B receptors.

From the Research

Medications Working via GABA-A Receptors

• Benzodiazepines, such as diazepam, alprazolam, bromazepam, and zolpidem, act by enhancing the inhibitory effects of GABA at GABA(A) receptors containing either an alpha1, -2, -3 or -5 subunit 4, 5, 6.
• Non-selective partial agonists, such as bretazenil, imidazenil, FG 8205, abecarnil, NS 2710, pagoclone, RWJ-51204, and (S)-desmethylzopiclone, have reduced intrinsic efficacy relative to full agonists and may have an improved preclinical pharmacological profile 4, 5.
• Efficacy selective compounds, such as L-838417, NGD 91-3, and SL651498, may interact with all four GABA(A) receptor subtypes and have partial rather than full agonist efficacies, or have comparable binding affinity but different efficacies at the various subtypes 4, 5.
• Chlornordiazepam, the major active metabolite of mexazolam, has a "pharmacodynamic fingerprint" that correlates better with an anxiolytic profile and fewer sedative effects, when compared to alprazolam, bromazepam, and zolpidem 6.

Medications Working via GABA-B Receptors

• There are no specific medications mentioned in the provided studies that work exclusively via GABA-B receptors. However, it is mentioned that GABA(B) receptors are targeted by some drugs, but the specific medications are not listed 7, 8.

Other Medications Affecting GABAergic Function

• Tiagabine and vigabatrin are novel antiepileptic drugs that act selectively through the GABA-ergic system, by inhibiting neuronal and glial uptake of GABA and increasing the synaptic concentration of GABA, respectively 7.
• Gabapentin, designed as a precursor of GABA, increases brain synaptic GABA and decreases influx of calcium ions into neurons via a specific subunit of voltage-dependent calcium channels 7.
• Conventional antiepileptics, such as carbamazepine, phenobarbital, phenytoin, and valproate, generally inhibit sodium currents or enhance GABA-ergic inhibition 7.