A Novel Positive Allosteric Modulator of the GABA-A Receptor - In Vivo Studies in Mice and Rats

The inhibitory neurotransmitter, GABA, is implicated in a number of seizure disorders. As a pentameric iontropic channel, GABA-A is a well-established therapeutic target to modulate inhibitory tone in the brain and provide seizure suppressive effects. However, many of the GABA-A modulators, such as benzodiazepines and barbiturates, are associated with significant sedative effects that reduce their suitability for chronic use in people with epilepsy. New treatments that can modulate the GABA-A receptor without sedating effects are thus in strong demand. This new study characterized the in vivo therapeutic response profile the the novel GABA-A positive allosteric modulator, ENX-101. Results suggest that this compound is well-tolerated and demonstrates minimal sedating effects at anticonvulsant doses, warranting further in vivo preclinical study and potential clinical evaluation in people with focal onset seizures.