The possibility of free radical reactions occurring in biological processes led 
to the development and employment of novel methods and techniques focused on 
determining their existence and importance in normal and pathological 
conditions. For this reason the use of nitrones for spin trapping free radicals 
became widespread in the 1970s and 1980s, when surprisingly the first evidence 
of their potent biological properties was noted. Since then widespread 
exploration and demonstration of the potent biological properties of 
phenyl-tert-butylnitrone (PBN) and its derivatives took place in preclinical 
models of septic shock and then in experimental stroke. The most extensive 
commercial effort made to capitalize on the potent properties of the 
PBN-nitrones was for acute ischemic stroke. This occurred during 1993-2006, when 
the 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, 
was shown to be safe in humans and was taken all the way through clinical phase 
3 trials and then was deemed to be ineffective. As summarized in this review, 
because of its excellent human safety profile, 2,4-disulfonylphenyl PBN, now 
called OKN-007 in the cancer studies, was tested as an anti-cancer agent in 
several preclinical glioma models and shown to be very effective. Based on these 
studies this compound is now scheduled to enter into early clinical trials for 
astrocytoma/glioblastoma multiforme this year. The potential use of OKN-007 in 
combination with neurotropic compounds such as the lanthionine ketamine esters 
is discussed for glioblastoma multiforme as well as for various other 
indications leading to dementia, such as aging, septic shock, and malaria 
infections. There is much more research and development activity ongoing for 
various indications with the nitrones, alone or in combination with other active 
compounds, as briefly noted in this review.