Studies on the 5-HT Receptor in Vascular Smooth Muscle

Changes in tension were monitored isometrically on spiral strips of freshly obtained bovine basilar arteries. Ergotamine (E), dihydroergotamine (DHE), methysergide (M) and pizotifen (BC-105) displaced the concentration-response curve for 5-HT in a noncompetitive way and in similar concentration ranges as indicated by the pD' 2(60 min) values of the three ergot alkaloids (E: 9.2, M: 9.1, DHE: 8.8) and the pD' 2(30 min) value (8.9) of BC-105. The ergot alkaloids but not BC-105 also exhibited considerable stimulating activity. The calculated pD2 values were 8.8 for E, 8.6 for DHE and 6.6 for M. Relative to 5-HT (= 1) the intrinsic activities were 0.4, 0.2 and 0.1 for E, DHE and M, respectively. BC-105 was nearly equipotent in antagonizing responses to 5-HT, E and DHE suggesting that both ergot alkaloids act as noncompetitive dualists at the 5-HT receptor. The results suggest that the strong stimulant rather than the blocking activity at the 5-HT receptor of ergotamine may be an important property for its therapeutic efficacy in migrainous attacks.