Serdaxin Active Ingredient Found to Enhance Neurotransmitter Release

Clavulanic acid, the active ingredient in Rexahn Pharmaceuticals’ Serdaxin, a drug in Phase II clinical development for major depressive disorder (MDD), enhances release of neurotransmitters in the brain such as dopamine by interacting with key proteins for vesicle trafficking and fusion, a study finds. The study was published online late last month in Neuroscience Letters.

Previous studies have shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodents and primates by a mechanism involving central nervous system (CNS) modulation, though its detailed mechanism of action has yet to be elucidated. To examine its potential as a CNS-modulating agent and its mechanism of action, researchers investigated effects of clavulanic acid in neuronal cells.

They found that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. They were also able to identify two proteins, Munc18-1 and RabR, that appear to bind to clavulanic acid and play a key role in neurosecretion and the vesicle trafficking process. An increase in translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid—treated cells.

According to the researchers, the data indicate that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders such as depression.

Source

Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking (abstract) [Neuroscience Letters]

Rexahn Pharmaceuticals Announces Publication of Study Validating Mechanism of Action of Serdaxin(R) [Rexahn Pharmaceuticals Press Release]