Pharmacologic properties of phenyl N-tert-butylnitrone.
Phenyl N-tert-butylnitrone (PBN) is the parent of a family of nitrones used as spin-trapping agents to trap free radicals. PBN's pharmacological effects in animal models are extensive, ranging from protection against death after endotoxin shock, protection from ischemia-reperfusion injury, to increasing the life span of mice. Recent additions to the list include protection from bacterial meningitis, thalidomide-induced teratogenicity, drug-induced diabetogenesis, and choline-deficient hepatocarcinogenesis. Because PBN reacts with oxygen radicals to produce less reactive species, it has been suggested that this is the basis of its pharmacological effects. However, there has been no hard evidence for this notation. Nevertheless, many investigators have used the presence of PBN's pharmacologic effect as evidence for free radical involvement in their models. Mechanistic studies on the PBN's antisepsis action revealed that PBN inhibits expression of various pro-inflammatory genes, suggesting that the protective action involves more than a straightforward free radical-scavenging mechanism. Previous and recent developments in the investigations on the pharmacologic properties of PBN are described in this review.
Kotake
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Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA. yashige-kotake@ouhsc.edu
D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003497:Cyclic N-Oxides; D016207:Cytokines / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D009589:Nitrogen Oxides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000188:drug therapy; D019097:Spin Trapping
D003497:Cyclic N-Oxides; D016207:Cytokines; D016328:NF-kappa B; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D009569:Nitric Oxide; C029217:phenyl-N-tert-butylnitrone