Selective Gelatinase Inhibitor
Neuroprotective Agents
Cross the Blood-Brain Barrier
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Abstract
SB-3CT, a potent and selective inhibitor of matrix metalloproteinase-2
and -9, has shown efficacy in several animal models of neurological
diseases. One of the greatest challenges in the development of therapeutics
for neurological diseases is the inability of drugs to cross the blood-brain
barrier. A sensitive bioanalytical method based on ultraperformance
liquid chromatography with multiple-reaction monitoring detection
was developed to measure levels of SB-3CT, its active metabolite,
the α-methyl analogue, and its <i>p</i>-hydroxy metabolite
in plasma and brain. The compounds are rapidly absorbed and are readily
distributed to the brain. The pharmacokinetic properties of these
gelatinase inhibitors and the efficacy shown by SB-3CT in animal models
of stroke, subarachnoid hemorrhage, and spinal cord injury indicate
that this class of compounds holds considerable promise in the treatment
of diseases of the central nervous system