[Pharmacological studies of celiprolol: I. Beta-blocking effect, intrinsic sympathomimetic activity, vasodilating and...

The beta-blocking effect, intrinsic sympathomimetic activity (ISA), and vasodilating and hypotensive effects of celiprolol were tested. 1. Celiprolol competitively antagonized the isoproterenol-induced positive chronotropic and inotropic effects in guinea pig right atrial and papillary muscles and isoproterenol-induced guinea pig tracheal relaxation with pA2 values of 8.03, 7.98 and 6.43, respectively. 2. In dogs, isoproterenol-induced increases in cardiac contractility and heart rate were markedly inhibited by celiprolol (83.1 and 84.8%, respectively), while isoproterenol-induced hypotension was suppressed only by 16.8%. 3. Celiprolol increased the beating rate of the right atrium and relaxed the trachea isolated from normal and reserpinized guinea pigs. Celiprolol also potentiated the contractility of the left atrium isolated from reserpinized animals. These effects of celiprolol were antagonized by propranolol. 4. Celiprolol concentration-dependently relaxed rat femoral arteries contracted by methoxamine. The concentration-relaxation curve was shifted to the right by pretreatment with propranolol. 5. Orally administered celiprolol produced long lasting hypotension in conscious SHR without any heart rate change. 6. These results indicate that celiprolol is a highly cardioselective beta-blocker with a significant ISA, which contributes to its vasodilatory and hypotensive effects.