SOME EFFECTS OF KÖ 1313 IN ANIMALS AND MAN

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Abstract
1 Kö 1313 competitively inhibited the increases in heart rate produced by isoprenaline in anaesthetized dogs. 2 Kö 1313 was 35 times more active than propranolol in blocking an isoprenaline induced tachycardia in anaesthetized dogs but only three times more active in blocking the increase in femoral blood flow produced by the injection of isoprenaline into the femoral artery. These observations suggest that Kö 1313 may have some cardio-selective activity. 3 When a series of doses of Kö 1313 was injected intravenously into anaesthetized dogs, the lower doses decreased heart rate while the larger doses increased heart rate. The same doses of propranolol reduced heart rate. 4 In lightly anaesthetized dogs, a series of doses of Kö 1313 progressively increased heart rate while propranolol produced little change. These observations indicate that Kö 1313 has slight intrinsic sympathomimetic activity. 5 The oral administration of Kö 1313 and propranolol had no effect on resting heart rate in man but reduced the increases produced by head-up tilt, standing and exercise.