Evidence that (+)-bupranolol interacts directly with myocardial beta-adrenoceptors. Control of optical purity with differential thermal analysis.
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.
D000818:Animals; D002046:Bupranolol / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D002415:Cats; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D009206:Myocardium / Q000378:metabolism*; D009905:Optical Rotatory Dispersion; D011412:Propanolamines / Q000378:metabolism*; D011433:Propranolol / Q000037:antagonists & inhibitors; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013696:Temperature
D011412:Propanolamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D002046:Bupranolol; D011433:Propranolol; D007545:Isoproterenol