Comparison of the effects of diltiazem and its analogue siratiazem on contractility in arteries, ileum and cardiac muscle.
1. The aim of this study was to compare the abilities of diltiazem and siratiazem to inhibit concentration-response curves for contractile responses to calcium in arterial and intestinal smooth muscle and cardiac muscle. 2. Diltiazem and siratiazem inhibited, in a concentration-dependent manner, the maximum contraction produced by cumulative addition of calcium chloride to rabbit mesenteric artery, ileum and paced atria in vitro. The order of potency, as indicated by the IC25 values (with 95% confidence intervals) for siratiazem was ileum, 0.33 microM (0-0.63) > mesenteric artery, 0.75 microM (0.32-1.01) and for diltiazem was ileum 0.1 microM (0.007-0.14) = mesenteric artery 0.13 microM (0-0.22). 3. In rabbit atria, the IC25 was of the order of 10 microM for both siratiazem and diltiazem. 4. Both drugs also inhibited calcium concentration-response curves in sheep cerebral arteries and in this tissue the IC25 values were 1.18 (0.37-1.63) and 0.89 (0-1.36) microM for siratiazem and diltiazem, respectively. 5. It is concluded that siratiazem, like diltiazem, blocks entry of calcium via voltage-operated channels with a similar potency to diltiazem on rabbit ileum and cardiac muscle and sheep cerebral arteries but is less potent on rabbit mesenteric arteries.
Panesar
M S
MS
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK.
Hagerty
M J
MJ
Kane
K A
KA
Wadsworth
R M
RM
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D011817:Rabbits; D012756:Sheep
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; C085176:siratiazem; D004110:Diltiazem; D002118:Calcium