The findings were published in the journal ACS Central Science. The researchers said their work points to a new strategy for tackling glutamate excitotoxicity, a process in which excessive levels of the neurotransmitter glutamate damage and kill nerve cells.

Glutamate is the main excitatory neurotransmitter in the central nervous system and plays a crucial role in learning and memory. However, excessive amounts can become toxic to neurons.

Under normal conditions, glutamate levels are tightly regulated by specialised transport proteins. A transporter known as EAAT2, found on astrocytes, removes excess glutamate from the extracellular space. When the transporter does not function properly, glutamate can accumulate and trigger excitotoxicity, leading to neuronal damage and cell death.

The mechanism has been linked to a range of neurological and neurodegenerative disorders, including epilepsy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis.

In the study, researchers used a strategy involving the replacement of hydrogen with deuterium, a stable isotope of hydrogen. The approach enabled them to develop a new generation of positive allosteric modulators (PAMs) targeting the EAAT2 transporter.

The resulting compounds showed favourable drug-like properties and strong anticonvulsant activity, the researchers said.

Electrophysiological studies also showed for the first time that compounds acting as allosteric activators of the EAAT2/GLT-1 transporter increased transporter currents in both mouse astrocytes and oocytes, providing evidence for the proposed mechanism of action, according to the study.

Professor Krzysztof Kamiński of the Department of Pharmaceutical Chemistry at Jagiellonian University Medical College said enhancing the removal of excess glutamate by improving the efficiency of the astrocytic EAAT2 transporter represented a new therapeutic approach.

He said the strategy focuses on astrocytes rather than neurons, targeting cells that play a key role in maintaining the environment necessary for proper neuronal function.

"We believe that this strategy will contribute to the development of innovative and well-tolerated therapies for diseases associated with glutamate excitotoxicity," he added.

The study was carried out by researchers from the Faculty of Pharmacy at Jagiellonian University Medical College, the Maj Institute of Pharmacology of the Polish Academy of Sciences, Maria Curie-Skłodowska University in Lublin, and partners in Europe and the United States, including Università degli Studi dell'Insubria, Drexel University College of Medicine, the University of Utah and the University of Washington School of Pharmacy.

The research was funded by Poland's National Science Centre. (PAP)

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