The inhibitory action of two thrombin inhibitors (TI-189 and TI-233) on the contractile responses to 5-hydroxytryptamine and prostaglandin endoperoxide analogue (U-44069) in isolated vascular strips.

1. Two arginine derivatives that were developed as thrombin inhibitors (TI-189 and TI-233) selectively inhibited the 5-hydroxytryptamine (5-HT)-induced contraction of rabbit aortic strips in a competitive manner. The PA2 values of TI-189 and TI-233 were 5.24 +/- 0.21 and 6.23 +/- 0.32 respectively. 2. Even at 10(-4) M they had no inhibitory effect on the contractile response to noradrenaline (NA), histamine, prostaglandin E2 (PGE2), PGF2 alpha, arachidonic acid or potassium in rabbit aortic strips. 3. In dog basilar and coronary arterial strips and also in rat fundus, both agents inhibited the 5-HT response in a non-competitive manner. 4. At 10(-5) M, TI-233 but not TI-189 antagonized effects of NA and KCl in the dog basilar and coronary arteries. 5. These arginine derivatives decreased the contractile responses induced by a prostaglandin endoperoxide analogue (U-44069) in rabbit aorta and in dog basilar and coronary arteries but there was no evidence for competitive antagonism. 6. These results indicate that the arginine derivatives are competitive antagonists selective for 5-HT receptors in rabbit aorta.