Tegaserod, a 5-HT4 receptor agonist, has been used to treat idiopathic constipation and constipation-predominant irritable bowel disease. It has recently been suggested that tegaserod has an affinity for 5-HT1B receptors, which mediate vasoconstriction. As some patients have experienced cardiac ischemia during treatment with tegaserod, we assessed contractions to tegaserod in healthy and diseased human isolated coronary arteries and compared the results with those obtained using sumatriptan, an established 5-HT1B receptor agonist. Proximal and distal human coronary arteries were divided into sets of healthy and diseased tissues based on functional endothelial responses. Concentration-response curves to tegaserod and sumatriptan were constructed to assess their contractile potential. Tegaserod's antagonist properties at 5-HT1B receptors were studied by constructing concentration-response curves to sumatriptan in the absence or presence of tegaserod (1 mu M). Sumatriptan induced concentration-dependent contractions, which were greater in distal than in proximal coronary artery segments. In the proximal segments, tegaserod induced contractions only at concentrations of 10 mu M or higher, while in distal segments contractions were generally absent. Tegaserod did not antagonize sumatriptan-induced contractions. There was no difference between the results obtained in healthy and diseased coronary arteries. In conclusion, tegaserod induced contractions in human proximal coronary arteries at concentrations 1000 times higher than C-max (6 mg bid). Hence, tegaserod does not exhibit a relevant vasoconstrictor potential in the human coronary artery. Further, tegaserod did not behave as an antagonist at 5-HT1B receptors. Additional studies may be warranted to investigate the use of 5-HT4 agonists in patients with cardiovascular risk factors. (C) 2009 Published by Elsevier B.V.