Antioxidative and thrombolytic TMP nitrone for treatment of ischemic stroke.
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.
Sun
Yewei
Y
Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou 510632, China.
Jiang
Jie
J
Zhang
Zaijun
Z
Yu
Pei
P
Wang
Linda
L
Xu
Changlin
C
Liu
Wei
W
Wang
Yuqiang
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy*; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009589:Nitrogen Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy
D000975:Antioxidants; D005343:Fibrinolytic Agents; D009589:Nitrogen Oxides; D011719:Pyrazines; C015388:nitrones; C017953:tetramethylpyrazine