COMPARATIVE STUDIES OF (−)‐, (±), (+)‐PROPRANOLOL, ATENOLOL, GUANETHIDINE, BRETYLIUM AND TETRACAINE ON ADRENERGIC TRANSMISSION

Abstract

1 Effects of (−)‐, (±)‐, and (+)‐propranolol, atenolol, guanethidine, bretylium and tetracaine were studied on relaxation responses of rabbit ileum and contractile responses of rabbit pulmonary artery and guinea‐pig vas deferens to electrical nerve stimulation (2 to 50 Hz) 2 In the ileum, inhibition by tetracaine 3.3 × 10⁻⁶M occurred at high frequencies of stimulation, while bretylium 1.2 × 10⁻⁴ M and guanethidine 2 × 10⁻⁵ M inhibited responses at all frequencies, the latter producing greater inhibition at low frequencies 3 (±)‐Propranolol 10⁻⁵ M produced a tetracaine‐type inhibition after 1 h and a bretylium‐pattern after 2 h in the ilea and pulmonary arteries and a transition from bretylium‐ to guanethidine‐pattern in the vas deferens, while atenolol 2 × 10⁻⁵ to 10⁻⁴M produced guanethidine‐type inhibition in all preparations 4 (−)‐, (±)‐, and (+)‐Propranolol 3 × 10⁻⁶ to 3.3 × 10⁻⁵M were equipotent in the vas deferens and ileum. However, inhibition by (−)‐propranolol 3.3 × 10⁻⁵ M persisted in the ileum, while that by the (+)‐isomer was partially restored by washing 5 (−)‐ or (+)‐Propranolol 3.3 × 10⁻⁵M or atenolol 2 × 10⁻⁵M did not inhibit relaxation of the ileum after the bath temperature was maintained at 4deg;C for 2 h during drug application 6 In conclusion, propranolol and atenolol both have gradually developing guanethidine‐like adrenergic neurone blocking actions.