Indole derivatives as neuroprotectants

It seems to be satisfactorily proved that reactive oxygen species (ROS) participate in numerous pathological processes in the nervous system (NS). Compounds able to interfere with the action of ROS might be useful in prevention and treatment of these pathologies. The search is focused on compounds with a suitable spectrum of pharmacological and pharmacokinetic properties, among which indole derivatives are distinct group with great potential to be further developed. The paper presents an overview of indole derived compounds in which protective action has been demonstrated in the NS in situations in which ROS are excessively generated, such as chemically induced oxidative stress, hypoxia/reoxygenation, ischemia/reperfusion. These compounds include indoleamines (melatonin), carbazoles (carvedilol), carbolines (tetrahydrocarbolines, pyrimidoindoles, vinpocetine). Special attention is paid to the gamma-carboline stobadine. A range of effects which seem to be associated with its neuroprotective actions (antioxidant and ROS scavenging effects, capability to pass the hematoencephalic barrier, pharmacokinetic properties, etc.) are considered. A novel compound with pyrimidoindole structure (U-101033E) is mentioned. Attention is drawn also to the neurotoxic potential demonstrated in some carbolines (2-amino-alpha-carboline, halogenated tetrahydro-beta-carboline "TaClo", harmane, norharmane). The indole nucleus seems to be a promising basis for design and synthesis of new derivatives able to protect the NS against oxidative stress in a variety of acute and chronic NS pathologies.