Compound 100

Compound 100 is a selective small molecule positive allosteric modulator (PAM) of the alpha 5 subunit-containing GABAA receptor (α5-GABAAR). Developed as a proprietary research compound by Roche, it is primarily used in preclinical studies to investigate the therapeutic potential of enhancing GABAergic inhibition in psychiatric disorders, specifically schizophrenia. The compound works by binding to an allosteric site on the α5-GABAAR, thereby increasing the receptor's response to the inhibitory neurotransmitter GABA. In the methylazoxymethanol acetate (MAM) rat model of schizophrenia, Compound 100 has demonstrated the ability to normalize aberrant dopamine neuron activity in the ventral tegmental area (VTA), suggesting a role in restoring the excitatory-inhibitory balance that is disrupted in the disease. It is frequently utilized as a comparative or confirmatory tool alongside other α5-GABAAR PAMs such as alogabat (RG1662).