The expanding role of antiplatelet agents in coronary artery disease. A current review of aspirin, glycoprotein IIb/IIIa inhibitors, and the thienopyridines.

The platelet has assumed an increasingly important role in cardiovascular medicine as our understanding of the pathophysiology of acute coronary syndromes (ACS) has evolved. Plaque rupture, platelet aggregation, and thrombus formation occur as a result of complex interaction between the platelet, the endothelium, and various inflammatory cells and circulating proteins. Aspirin continues to form the foundation of any anti-ischemic regimen, but cardiologists have long recognized the need for newer, more potent antiplatelet agents. Glycoprotein IIb/IIIa receptor antagonists and thienopryidines have been developed over the past decade and now serve as powerful complements to aspirin in the prevention and treatment of coronary events. The paper will begin with a review of aspirin as well as a discussion of the concept of aspirin resistance. The rapidly expanding body of knowledge supporting the use of glycoprotein IIb/IIIa receptor blockers and thienopyridines will then be addressed, with an emphasis on reconciling recent controversies in the literature. Future advances in the treatment of coronary artery disease will likely occur as we further refine the role of these established antiplatelet drugs and develop agents that bind to novel targets in the thrombotic cascade.

Sex differences in dopamine receptor overproduction and elimination.

Density of dopamine D1 and D2 family receptors was assessed using autoradiography in male and female rats from 25 to 120 days of age, focusing on transitions through puberty into full adulthood. Males had greater overproduction (approximately 4.6-fold) and elimination of striatal D1 and D2 receptors than females, though their adult densities were very similar. Males had more extensive overproduction of D1 receptors in nucleus accumbens and sustained a greater density into adulthood (57.8 +/- 21.2%). These results have implications for understanding gender differences in the prevalence of clinical disorders associated with dopamine.

Evidence for dopamine receptor pruning between adolescence and adulthood in striatum but not nucleus accumbens.

Postnatal development of dopamine D1 and D2 receptor families in striatum and nucleus accumbens of rats was studied at 25, 35, 40, 60, 80, 100 and 120 days using autoradiography. These ages were selected to test the hypothesis that dopamine receptors were overproduced prior to puberty (day 40), and pruned back to adult levels thereafter. This hypothesis was confirmed in striatum but not nucleus accumbens. D1 receptor Bmax ([3H]SCH-23390) peaked at 40 days, with levels 67 +/- 21% greater than at 25 days. However, Bmax levels were at least 35% lower at 60-120 days than at 40 days. Similarly, D2 receptor numbers ([3H]YM-09151-2) increased 144 +/- 26% between 25 and 40 days, but were reduced by 34-38% between 60-120 days. In contrast, D1 and D2 receptor Bmax increase approximately 150% between 25 and 40 days in nucleus accumbens, levels fell slightly at 60 or 80 days, but were no different at 100 and 120 days then they were at 40 days. These findings suggest that these two major dopamine target regions follow different developmental strategies, and this has implications for etiological theories of schizophrenia that focus on anomalous receptor pruning.