Neuroprotection by the pyridoindole stobadine: a minireview.
The minireview summarizes data documenting that pyridoindole stobadine (STB) may protect nervous structures against oxidative stress. This was demonstrated by the impairment of synaptic transmission in hippocampal slices and sympathetic ganglia exposed to hypoxia/reoxygenation (H/R) in vitro as well as by survival of rats and dogs exposed to brain ischemia/reperfusion (I/R) in vivo. The STB effect was linked mostly to its free radical scavenging and antioxidant properties. STB seems to act primarily on phospholipids, thus protecting the integrity and function of somatic membranes in neurons as well as those in subcellular organelles, such as mitochondria and endoplasmic reticulum. STB prevented damage to Ca2+ sequestering systems in endoplasmic reticulum and synaptosomes induced by lipid peroxidation initiators. It was found to diminish changes in NMDA and adrenergic alpha1-receptors evoked in the brain by I/R or H/R. The compound prevented total thiols, participating in tissue antioxidative protection, from decreasing in brain under these conditions. It readily penetrates into both the hydrophilic and the hydrophobic compartments of the CNS. Data were obtained indicating that in I/R, protection of structures such as brain-blood vessels, endothelium, and/or erythrocytes may participate in the STB effect, besides the direct protection of nervous tissue. STB may be characterized as a potential protectant of the CNS in diseases in which oxidative injury may play an important role, for example, stroke, neurotrauma, chronic brain ischemia, or some neurodegenerative diseases. Its molecule could provide a useful model in the further search for novel compounds with even more pertinent pharmacological and pharmacokinetic profiles.
Stolc
S
S
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Vlkolinský
R
R
Pavlásek
J
J
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D004285:Dogs; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000517:prevention & control*; D009435:Synaptic Transmission / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology
D002243:Carbolines; D007473:Ion Channels; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C100106:dicarbine