Pharmacological properties of new 1,2-benzisothiazolyloxypropanolamines on cardiac and tracheal beta-receptors.
This paper reports the pharmacological assessment of beta-blocking properties of new benzisothiazole and benzisoxazole derivatives, substituted in position 3-, 5- or 7- with the oxypropanolaminic side chain (I-VI), to of which contain the -OCH3 group in position 3- (III, V) in comparison with propranolol. The results, obtained on isoprenaline-induced chronotropic response of rat isolated atria and on isoprenaline-induced relaxation of guinea-pig tracheal strips precontracted by carbachol, suggest that the compounds (I, II, IV, VI), at variance with the methoxy-substituted (III, V), possess a beta 1-blocking activity 4-300 times lower than propranolol. pA2 values drop from 8.36 to 7.56 and 7.04 from the relative compounds substituted in position 7- (IV), 3- (I) and 5- (II), thus indicating that the position of the oxypropanolaminic chain in the benzisothiazole ring affects the ability of the molecules to interact with the beta 1-adrenoceptor. Furthermore, benzisothiazole rather than benzisoxazole ring seems to facilitate the drug-beta 1 adrenoceptor interaction, the compound (I) displaying a 10-fold higher affinity than compound (VI).
Barocelli
E
E
Istituto di Farmacologia e Farmacognosia, Facoltà di Farmacia, Università di Parma.
Chiavarini
M
M
Ballabeni
V
V
Mingiardi
M R
MR
Morini
G
G
Ronchini
F
F
Impicciatore
M
M
D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009206:Myocardium / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D013844:Thiazoles; D002217:Carbachol; D011433:Propranolol; D007545:Isoproterenol