Brain stroke is one of the leading causes of death worldwide, with ischemic mechanism (blood flow obstruction) generating up to 90% of stroke cases. Oxygen-glucose deprivation (OGD), the main effect of ischemia, leads to depletion of intracellular ATP, hence loss of the ATP-dependent glutamate uptake by glutamate transporters. This, in turn, induces excitotoxicity due to excessive amounts of glutamate in extracellular space. Thus, the obvious treatment strategy is hyperactivation of inhibitory receptors, e.g. GABAA receptors (GABAARs) and downregulation of excitatory glutamate receptors, first of all those of NMDA type (NMDRs). However, the use of GABAAR and NMDAR selective ligands with high activity is associated with deleterious side effects such as impaired functional recovery after stroke1 and symptoms of psychosis2. Hence, there remains a pressing demand for medications that counteract ischemia-induced excitotoxicity with lowered side effects. In our study we tested ß-alanine (Ala) as a perspective protector from neural cell ischemic damage. Ala induces inhibition via action at glycine receptors and GABAARs, and suppresses excitation by competing (as a partial agonist) with glycine at its co-agonist binding site on NMDARs3. We have tested Ala’s effects on two types of neurons: cerebellar granule cells (CGCs) and Purkinje cells (PCs). To reproduce ischemic damage, murine cerebellar slices were perfused with solution containing 10 mM sucrose (to replace 10 mM glucose required for normal perfusion solutions) and gassed with 95%N2/5%CO2 (to produce low O2 insult). To quantify the effect of Ala on neural cell functioning we used whole-cell patch-clamp to register the amplitude of anoxic depolarization of cell membrane (AD) which follows OGD development. We found that application of 1 mM Ala reduces significantly the AD amplitude. In mV, for CGCs: from 12.12±0.79 (n=12) to 7.56±0.58 (n=11), P=1.4*10-4; in PCs: from 39.25±2.71 (n=14) to 24.1±1.77 (n=14), P=1.1*10-4, Student’s t-test for both comparisons. To test the impact of Ala on cell survival, we used imaging of fluorescence generated by propidium iodide (marks dead cells) in a course of OGD in cerebellar CGC layer. To analyze experimental data, we used two-way repeated measures analysis of variance for time (factor 1) and experimental action (control conditions, OGD, OGD+Ala – factor 2). We found that factor 2 and the combination of factor 1 ´ factor 2, but not factor1, cause a significant impact: factor 1, F(1.62, 11.04)=1.202, P=0.33; factor 2, F(2, 12)=6.72, P=0.011; factor 1 × factor 2, F(46, 157)=1.56, P=0.023. Tukey test on factor 2: P<1*10-4 for Control vs. OGD and for OGD vs. OGD+Ala, P=0.075 for Control vs. OGD+Ala. The traditional approach to developing novel pharmacological therapies involves designing drugs that display a single activity profile at a very high potency, thus creating a unidirectional "silver bullet" that interacts with a single drug target. However, the simultaneous modulation of several drug targets at lower potency may provide a superior therapeutic index for multi-mechanism conditions like ischemic stroke4. This makes Ala, which reduces significantly ischemic damage of neural cells via simultaneous suppression of excitatory receptors and upregulation of inhibitory receptors, a promising candidate for ischemic stroke treatment.