Antioxidative and thrombolytic TMP nitrone for treatment of ischemic stroke

Bioorg Med Chem. 2008 Oct 1;16(19):8868-74. doi: 10.1016/j.bmc.2008.08.075. Epub 2008 Aug 31.

Abstract

Ischemic stroke results from brain blood vessel blockage by thrombus, and produces neuronal cell damage and death. While thrombolytic therapy with tPA has achieved some success in clinic, the strategy of using neuroprotective agents to treat ischemic stroke has been disappointing thus far. In the present work, we synthesized TBN, a derivative of the clinically useful stroke drug TMP armed with a powerful free radical-scavenging nitrone moiety. TBN retains the thrombolytic activity of the parent TMP and possesses strong antioxidative properties. TBN demonstrates significant activity in the rat MCAo stroke model. The results suggest that design of molecules possessing both thrombolytic and neuroprotective properties may be a novel strategy for effective stroke therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Brain Ischemia / drug therapy*
  • Fibrinolytic Agents / pharmacology
  • Fibrinolytic Agents / therapeutic use*
  • Nitrogen Oxides / pharmacology
  • Nitrogen Oxides / therapeutic use*
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use*
  • Rats
  • Stroke / drug therapy*
  • Thrombolytic Therapy

Substances

  • Antioxidants
  • Fibrinolytic Agents
  • Nitrogen Oxides
  • Pyrazines
  • nitrones
  • tetramethylpyrazine