Evidence that (+)-bupranolol interacts directly with myocardial ?-adrenoceptors

Abstract

Melting points measured with the capillary method were 150.5 degree C, 150.5 degree C and 224.0 degree C for hydrochlorides of (+)-bupranolol, (-)-bupranolol and (+/-)-bupranolol, respectively. The large difference in melting points of 73.5 degree C prompted us to determine possible contaminations of (+)-bupranolol with traces of (-)-bupranolol using differential scanning calorimetry. We detected as little as 0.001% (-)-bupranolol in a standard mixture of (+)-bupranolol and (-)-bupranolol. A batch of (+)-bupranolol not measurably contaminated with (-)-bupranolol (optically purity greater than 99.999%) was used in pharmacological and biochemical assays. The affinities of (-)-bupranolol and (+)-bupranolol were determined functionally by the blockade of isoprenaline stimulation of spontaneously beating rat right atria and electrically driven kitten papillary muscles; and directly by inhibition of binding of 3H-(-)-propranolol to kitten ventricle membrane particles. In all 3 systems the enantiomeric (-)/(+) affinity ratio was 50--120 for bupranolol. These experiments prove that (+)-bupranolol itself binds to the beta-adrenoceptors of mammalian myocardium.

The effects of the stereoisomers of propafenone and diprafenone in guinea‐pig heart

“…Binding to fi-adrenoceptors is characterized by a high degree of stereoselectivity (Kaumann & Birnbaumer 1974;Wachter et al, 1980;Lemoine & Kaumann, 1983; Morris & Kaumann, 1984). There is also evidence for stereoselective The asymmetric carbon atom is indicated by an asterisk.…”

The β1 and β2‐adrenoceptor affinity and β1‐blocking potency of S‐ and R‐metoprolol

“…Thus, due to the possible contamination of the R-enantiomer with significant quantities of the S-form, conclusions regarding the actual fl-adrenoceptor affinity of the R-form could not be drawn from these studies. One exception is a study by Kaumann and coworkers (Wachter et al, 1980), demonstrating that the R-form of bupranolol (enantiomeric purity >99.9%) is about 100 times less potent as a fl-blocker compared to the corresponding S-form. Results obtained in a number of studies suggest that the steric requirements of the fl1-adrenoceptor is more stringent than that of the #2-adrenoceptor (Lemoine & Kaumann 1983; Morris Walter et al, 1984;Nathanson, 1988). Indeed, Nathanson (1988) demonstrated a marked potency of R-timolol (enantiometric purity >99.9%) to antagonize the #2-adrenoceptor stimulant effect of isoprenaline in the rabbit ciliary process.…”