The importance of NMDA antagonists in animal models of ischemic injury and major depressive disease

Glutamatergic system is the main excitatory system and glutamatergic receptors are the most abundantly expressed in whole central nervous system. The most widespread type of glutamatergic receptors are N-methyl-D-aspartate (NMDA) receptors which are essential for physiological development of nervous tissue, synaptic plasticity and cognitive processes. On the other hand, over-activation of these receptors leads to excitotoxic damage of nervous tissue and serious neurological consequences for future quality of life. Disruption of glutamatergic system is common feature for hypoxic-ischemic damage, traumatic brain injury, neurodegenerative and neuropsychiatric diseases. Therefore glutamatergic system and specifically NMDA receptors are an attractive target for neuropharmacological research. Presented thesis explores the effect of several molecules with modulating inhibiting effect on NMDA receptor. Work is preferentially focused on application research; the main aim is evaluated therapeutic potential of studied compounds. First group of compounds is represented by neuroactive steroids pregnanolone glutamate and pregnanolone hemipimelate, which are allosteric inhibitors of NMDA receptor. Here, their neuroprotective effect is demonstrated in hypoxic-ischemic and excitotoxic damage of nervous tissue...