ABSTRACT
GABA is a major inhibitory neurotransmitter that regulates the balance between excitatory and inhibitory circuits in the human nervous system. The GABA receptors are divided into three main subtypes, GABAA , GABAB , and GABAC (also termed GABAA rho) receptors. GABAA receptors are pentameric ligand-gated ion channels widely expressed throughout the central and peripheral nervous system. The activation of GABAA receptors results in opening of an anion-selective channel that mainly gates chloride ions and allows them to flow into the neuron, causing hyperpolarization of the cell membrane that dampens neural excitability. This makes GABAA receptors critical anaesthetic and analgesic targets for existing as well as for the development of novel drugs. In this review, we first summarize the biochemical properties of GABAA receptors and the clinical anaesthetics and analgesics targeting the receptors. In a forward-looking section, we summarize the emerging role of GABAergic signalling in treatment of COVID-19 related infections. Finally, we discuss the opportunities arising from targeting specific and unique subunit interfaces for the development of novel anaesthetics and analgesics leading to more efficient therapies.