Bis-arenoxypropanolamines as potential beta-adrenolytics: a reinvestigation.
A number of symmetrical as well as asymmetrical bis-arenoxypropanolamines have been synthesized and evaluated for their beta-adrenolytic properties. The pharmacological characterization of these compounds was performed in vitro by direct studies (3H-dihydroalprenolol was used as the specific ligand for beta-receptors), and by determining the beta-blocking capacity on isoproterenol (ISO)-induced increased heart rate (isolated guinea-pig atrium); and in vivo by evaluating the antagonism on ISO-induced hypotension and tachycardia, as well as the intrinsic sympathomimetic activity (ISA) on reserpinized and vagotomized rats. The best result was observed with the simplest derivative, i.e. the bis-phenoxypropanolamine compound, which shows in vitro and in vivo potencies almost comparable to propranolol and, moreover, significant bronchodilating activity.
Da Re
P
P
Department of Pharmaceutical Sciences, University of Bologna, Italy.
Valenti
P
P
Fabbri
G
G
Frigeni
V
V
Reggiani
A
A
Della Bella
D
D
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis*; D000758:Anesthesia; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D011412:Propanolamines / Q000138:chemical synthesis* / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D014628:Vagotomy
D000319:Adrenergic beta-Antagonists; D001993:Bronchodilator Agents; D008688:Methacholine Compounds; D011412:Propanolamines; D012110:Reserpine; D011433:Propranolol