Effect of MCI-176, a new calcium channel blocker, on large and small coronary arteries in dogs.
MCI-176, a new calcium channel blocker, increases coronary blood flow and may improve perfusion in ischaemic areas. Its vasodilating effects on large conductive coronary arteries and the resistive arterioles were therefore compared with those of diltiazem, nifedipine, glyceryl trinitrate and adenosine in anaesthetised open chest beagle dogs. Intracoronary injection of these compounds caused dose dependent increases in coronary flow associated with decreases in the resistance of resistive arterioles, and the rank order of potency was nifedipine greater than adenosine greater than MCI-176 greater than diltiazem greater than glyceryl trinitrate. The resistance of the large conductive vessels was likewise reduced by these agents, except for adenosine. Glyceryl trinitrate showed the highest selectivity to the large conductive vessels, while adenosine showed the lowest and calcium channel blockers were intermediate. Among three calcium channel blockers, MCI-176 had the highest selectivity to the large conductive vessels, while the duration of action was the longest with diltiazem; the duration of action of MCI-176 was intermediate. Thus, MCI-176 is a coronary vasodilator, the potency of which is intermediate between nifedipine and diltiazem, but it has the highest selectivity to the large conductive vessels among these three compounds.
Ishibashi
T
T
Department of Pharmacology, Niigata University School of Medicine, Japan.
Nakazawa
M
M
Imai
S
S
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008297:Male; D011799:Quinazolines / Q000494:pharmacology*; D052999:Quinazolinones; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D011799:Quinazolines; D052999:Quinazolinones; D014665:Vasodilator Agents; C050606:MCI 176; D000241:Adenosine