Spiro Hydantoins Can Reverse the Action of Positive Allosteric Modulators on GABA_ARs.

ABSTRACT: GABA_ARs are the most abundant inhibitory neuroreceptors. Drugs that enhance their action are used to treat epilepsy, anxiety, and other conditions. Benzodiazepines can exert a range of allosteric interactions from positive to negative, but they only act on γ-subunit containing GABA_ARs. Agents acting in the transmembrane domain can interact with a wider range of GABA_ARs, but they exert only positive allosteric actions, and their therapeutic actions are often limited by sedation because their binding sites are the same as those used by general anesthetics. Consequently, their therapeutic action is limited by sedation. We report the synthesis and pharmacological evaluation of several novel spiro-hydantoins that do not modulate orthosteric agonist binding but d

SUBMITTER: Koinas DA 

PROVIDER: S-EPMC12516361 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature