Experiments in animals on the pharmacological effects of metipranolol in comparison with propranolol and pindolol.
The beta-blocking agent 1-(4-acetoxy-2,3,5-trimethylphenyloxy)-3-isopropylamino-propan-2-ol (metipranolol) was compared with propranolol and pindolol. The beta-blocking activity on isoproterenol induced tachycardia was determined in rabbits (ED250bpm). The following doses in microgram/kg i.v. were required to produce the same inhibition: 410 propranolol; 160 metipranolol; 130 pindolol. When intrinsic sympathomimetic activity was determined in reserpinized rats metipranolol was found to produce less than 10% of the increase in heart rate induced by a standard isoproterenol dose (1 mg/kg i.p.), whereas propranolol caused less than 20% and pindolol ca. 60%. The membrane stabilising activity, determined by the elevation of the fibrillation threshold (ED delta100muA) in rabbit hearts, was found to be greatest with propranolol (0.98 mg/kg i.v.) and least with metipranolol (1.68 mg/kg), with pindolol occupying an intermediate position (1.10 mg/kg). The cardioprotective action to hypoxia stress of metipranolol in rats was found to be the best, requiring a dose of only 5 microgram/kg i.p. compared with values of 28 microgram/kg for pindolol and 250 microgram/kg for propranolol. These results show that metipranolol has a high beta-sympatholytic activity which is not accompanied by either marked intrinsic activity or membrane-stabilising properties. The relatively marked cardioprotective action, which is probably due to a metabolic action, is particularly noteworthy.
Experiments in animals on the pharmacological effects of metipranolol in comparison with propranolol and pindolol. The beta-blocking agent 1-(4-acetoxy-2,3,5-trimethylphenyloxy)-3-isopropylamino-propan-2-ol (metipranolol) was compared with propranolol and pindolol. The beta-blocking activity on isoproterenol induced tachycardia was determined in rabbits (ED250bpm). The following doses in microgram/kg i.v. were required to produce the same inhibition: 410 propranolol; 160 metipranolol; 130 pindolol. When intrinsic sympathomimetic activity was determined in reserpinized rats metipranolol was found to produce less than 10% of the increase in heart rate induced by a standard isoproterenol dose (1 mg/kg i.p.), whereas propranolol caused less than 20% and pindolol ca. 60%. The membrane stabilising activity, determined by the elevation of the fibrillation threshold (ED delta100muA) in rabbit hearts, was found to be greatest with propranolol (0.98 mg/kg i.v.) and least with metipranolol (1.68 mg/kg), with pindolol occupying an intermediate position (1.10 mg/kg). The cardioprotective action to hypoxia stress of metipranolol in rats was found to be the best, requiring a dose of only 5 microgram/kg i.p. compared with values of 28 microgram/kg for pindolol and 250 microgram/kg for propranolol. These results show that metipranolol has a high beta-sympatholytic activity which is not accompanied by either marked intrinsic activity or membrane-stabilising properties. The relatively marked cardioprotective action, which is probably due to a metabolic action, is particularly noteworthy.