Dihydropyridine composition

Pharmaceutical composition of certain dihydropyridine compounds and salts thereof are provided which exhibit both Ca.sup.2+ -antagonistic and adrenergic beta-receptor blocking activities and therefore are useful for the treatment of ischemic heart diseases and hypertension. The pharmaceutical compositions contains either 4-(2-hydroxy-3-phenoxy-propylamino)-butyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate or 6-(2-hydroxy-3-phenoxypropylamino) hexyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate or their pharmaceutically acceptable salts.

It is known that certain dihydropyridine derivatives have a Ca.sup.2+ 
-antagonistic action, and are highly useful for treatment of various 
cardiovascular disorders such as angina pectoris, myocardial infarction, 
hypertension and cardiac arrythmia. It is further known that 
beta-adrenoceptor blocking agents are also useful for the treatment of 
such cardiovascular disorders. 
However, the mechanism of actions of dihydropyridine derivatives is 
entirely different from that of beta-adrenocaptor blocking agents. That 
is, beta-adrenoceptor blocking agents reduce heart rate, cardiac output, 
stroke volume, cardiac work and myocardial oxygen demand whereas, 
Ca.sup.2+ -antagonists improve left ventricular function due to their 
coronary vasodilating and systemic vasodilating effect (reduction in 
afterload) and also inhibit coronary vasospasm. 
Recently it has been reported that a combined administration of a Ca.sup.2+ 
-antagonist and a beta-blocker can achieve maximal symptomatic improvement 
in clinical angina pectoris. [Bassan, M., Wiler-Ravell, D. and Shalev, O.; 
Additive antianginal effect of verapamil in patients receiving 
propranolol; Br. Med. J., 284, 1067 (1982)]. Further it has been reported 
that a combined administration of such two kinds of drug can be 
recommended for the treatment of hypertension, since the side effects of 
either drug are almost abolished or inhibited by the combination 
administration of both drugs. That is, beta-blocker inhibits a Ca.sup.2+ 
-antagonist-induced reflex increase of heart rate; and beta-blocker 
completely inhibit a Ca.sup.2+ -antagonist-induced increase of plasma 
renin activity. [Aoki, A., Kondo, S., Mochizuki, A., et al; 
Antihypertensive effect of Cardiovascular Ca.sup.2+ -antagonist in 
hypertensive patients in the absence and presence of beta-adrenergic 
blockade; Am. Heart J., 96, 218 (1978)] 
Thus, it would be expected that a compound having both Ca.sup.2+ 
-antagonistic and beta-blocking activities are of interest in the 
management of ischemic heart-diseases and hypertension. 
However, any compound having such both actions is not known until now. That 
is, it has never been reported that a compound having both Ca.sup.2+ 
-antagonistic and beta-blocking activities has been synthesized. Thus the 
purpose of this invention is to provide novel compounds which have both 
the actions (namely, Ca.sup.2+ -antagonistic activity and adrenergic 
beta-receptor blocking activity) and the production methods for the 
compounds.