AMPA receptors: molecular mechanisms of synaptic plasticity and the potential of Ampasse in addressing cognitive impairment

Dysfunction of the glutamatergic system, specifically involving AMPA receptors, is recognized as a significant pathogenic mechanism underlying cognitive impairment. AMPA glutamate receptors mediate fast excitatory postsynaptic currents in the majority of brain synapses and play a crucial role in the processes associated with long-term potentiation, which is integral to memory function. Additional mechanisms of synaptic plasticity linked to AMPA receptors include long-term depression of synaptic transmission, homeostatic plasticity, and AMPA receptor trafficking. Ampasse (calcium hydroxynicotinoyl glutamate) is an ampakine that acts as a positive allosteric modulator of AMPA receptors, thereby facilitating its procognitive effects. Radioligand analyses have confirmed Ampasse's binding to AMPA receptors. Ampasse has been shown to dose-dependently enhance synaptic transmission in the Schaffer collateral-CA1 pyramidal neuron system of the hippocampus in vivo. The neuroprotective potential of Ampasse has been demonstrated in experimental studies investigating its effects on neurodegenerative changes following acute hemorrhagic stroke. The positive impact of Ampasse on cognitive functions, along with its safety profile, has been demonstrated in both animal models and clinical trials involving patients with chronic cerebral ischemia, as well as during the early and late phases of recovery following ischemic stroke.