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Afobazole 5-ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole] is an anxiolytic drug which was developed in Zakusov Institute of Pharmacology RAMS and is currently in clinical use in Russia. In ex vivo experiments it was established that afobazole is able to prevent stress induced decrease in brain benzodiazepine receptor binding in animals exposed to different fear conditions – brightly lighted open field, odor of predator etc. Receptor profile study revealed that afobazole interacts with sigma ?1 (Ki= 5.9x10-6 M), melatonin ??1 (Ki= 1,6x10-5 ?) and ??3 (Ki= 9,7x10-7 ?) receptors as well as with regulatory site of monoaminooxidase MAO-? (Ki= 3,6x10-6 ?). Afobasole (10-8 ?) was found to promote mobilization of ?1- receptors to the plasma membrane from endoplasmic reticulum in HT-22 cells, which is also proving afobazole-?1-receptors interaction. ?1-receptors are known to modulate various processes that contribute to neuroprotection during pathophysiological states, in particular neuronal ischemia. Based on these several in vitro and in vivo experiments were performed to investigate neuroprotective properties of afobazole. In vitro in HT-22 neuronal cells afobazole (10-8 - 10-6M) was shown to decrease neuronal death in response to oxidative stress and glutamate excitotoxicity. Afobazole decreased caspase-3 activity in the model of glutamate excitotoxicity and increased BDNF (brain derived nerve factor) and NGF (nerve growth factor) levels in HT-22 cells. Ex vivo afobazole prevented stress-induced decrease in BDNF level in brain structures of BALB/c mice, reduced NO production and increased the activity of succinate dehydrogenase in ischemic brain. Several studies proved afobazole to be neuroprotective ex vivo and in vivo in stroke models. In rats undergoing photothrombosis of vessels in the prefrontal cortex application of afobazole 1 h after the ischemic stroke and for 8 days thereafter reduced stroke volume by 50%. In the stroke model of middle cerebral artery occlusion treatment with afobazole at the dose range of 0.1-5.0 mg/kg which started 6-24h after surgery also significantly decreased lesion volume. In hemorrhagic stroke models (acute and repeated posttraumatic hematoma) afobazole when administered 3 to 6 h after the onset of stroke and then twice daily for two weeks increased survival, declined the neurological deficits scores and improved recovery of cognitive functions. The in vitro data suggests afobazole activation of ?1- receptors may contribute to its properties to enhance neuronal survival and neuroprotective effects in stroke models. The results obtained provide evidence to extend the indications for treatment with afobazole in clinical practice.