PT  - JOURNAL ARTICLE
AU  - T Asano
AU  - H Hidaka
TI  - Intracellular Ca++ antagonist, HA1004: pharmacological properties different from those of nicardipine.
DP  - 1985 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 454--458
VI  - 233
IP  - 2
4099  - http://jpet.aspetjournals.org/content/233/2/454.short
4100  - http://jpet.aspetjournals.org/content/233/2/454.full
SO  - J Pharmacol Exp Ther1985 May 01; 233
AB  - Pharmacological properties of N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), a newly synthesized intracellular Ca++ antagonist, were studied by comparing its cardiovascular actions with those of nicardipine, a Ca++ entry blocker. Both i.a. and i.v. injections of HA1004 produced a dose dependent increase in vertebral, coronary and renal blood flow, respectively, in pentobarbital-anesthetized dogs. Continuous infusion of atropine, propranolol or aminophylline exerted no significant effect on the HA1004-induced vasodilation. A Ca++ entry blocker, nicardipine, increased vertebral and coronary blood flow after injections but did not produce an increase in renal blood flow, thereby suggesting notable differences between the cardiovascular effects of HA1004 and the Ca++ entry antagonist, nicardipine. HA1004 inhibited KCl, phenylephrine and prostaglandin F2 alpha-induced contraction of isolated canine renal arterial preparations, in a dose-dependent fashion, whereas nicardipine was much less effective in blocking the contraction of the preparations induced by phenylephrine and prostaglandin F2 alpha. HA1004 inhibited the phenylephrine-induced contraction of the renal artery in the absence of Ca++. HA1004 neither depressed the amplitude nor the duration of the slow action potentials of isolated guinea-pig hearts. These results suggest that HA1004 is a Ca++ antagonist of different class from Ca++ entry blockers such as nicardipine.