Commonly Used Therapeutics Associated with Changes in Arousal Inhibit GABA_AR Activation.

ABSTRACT: GABA_A receptor-positive modulators are well-known to induce sedation, sleep, and general anesthesia. Conversely, GABA_A receptor negative allosteric modulators (GABA_ARNAMs) can increase arousal and induce seizures. Motivated by our studies with patients with hypersomnia, and our discovery that two GABA_ARNAMs can restore the Excitation/Inhibition (E/I) balance in vitro and arousal in vivo, we chose to screen 11 compounds that have been reported to modulate arousal, to see if they shared a GABA-related mechanism. We determined modulation with both conventional and microfluidic patch clamp methods. We found that receptor activation was variably modulated by all 11 compounds: Rifampicin (RIF), Metronidazole (MET), Minocycline (MIN), Erythromycin (ERY)

SUBMITTER: Kaplan A 

PROVIDER: S-EPMC9953295 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature