Joel Morris* and Ronald J. Shebuski Pages 469 - 482 ( 14 )
This review is dedicated to small molecule approaches to prevention of restenosis (the chronic renarrowing of a previously balloon-dilated site in the vasculature). Since the platelet fibrinogen GPIIb/IIIa receptor has gained much attention due to the development of ReoPro® for the prevention of "abrupt closure" in high risk angioplasty patients, a great deal of discussion in this review is dedicated to small molecule antagonists of the GPIIb/IIIa receptor. Attention is also focussed on anti proliferative agents and anti-oxidants intended to impact smooth muscle cell proliferation and migration. The prototypic anti-proliferative described is the 2-arninocbromone, U-86983. Also addressed is the important area of classical receptor antagonism with agents such as DUP753 (Losartan, Cozaar) directed against the angiotensin II, subtype 1 receptor (AT-I) and Ro46-2005 and SB209670 directed against the endothelin type I receptor (ET-1). Finally, a discussion is included of agents directed towards the synthesis or liberation of nitric oxide as a means to positively influence the vascular response to injury. Also discussed are miscellaneous drugs that may impact vascular restenosis such as trapidil, taxol, carvedilol, ciprostene, Na+-H+ exchangers, and lastly, tryrosine kinase inhibitors.