Comparative Studies of (−)‐, (±), (+)‐propranolol, Atenolol, Guanethidine, Bretylium and Tetracaine on Adrenergic Transmission

Abstract

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) 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 (±)‐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 (−)‐, (±)‐, 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 (−)‐ 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 In conclusion, propranolol and atenolol both have gradually developing guanethidine‐like adrenergic neurone blocking actions.

Exercise‐induced increments in plasma levels of propranolol and noradrenaline.

“…A further consequence of the interaction of propranolol with adrenergic nerve endings could be altered storage and release of noradrenaline. In animal studies, propranolol has been suggested to decrease noradrenaline release, whether by blockade of presynaptic 8-receptors (Adler-Graschinsky & Langer, 1975), a neuronal blocking effect (Saelens et al, 1977;Kaiho et al, 1981), or a central mechanism (Privitera et al, 1979). Insofar as plasma noradrenaline levels reflect the release of neurotransmitter, the data from the present study do not support diminished neurotransmitter release during treatment with propranolol.…”

The distribution of (-)-propranolol in the isolated rabbit iris

“…Though widely used, their mechanism of action is not fully understood. These blockers decrease the production of aqueous humor (1), but what is the pharmacological principle behind it: beta-adrenoceptor-blockade, local anaesthetic effect or adrenergic neurone blockade (2,3,4)?…”