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Differential time course of the vasodilator action of various calcium antagonists
Author(s) -
Lee R,
Kam KL,
Pfaffendorf M,
Zwieten PA
Publication year - 1998
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1998.tb00993.x
Subject(s) - mibefradil , verapamil , lacidipine , vasodilation , nifedipine , pharmacology , chronotropic , lercanidipine , isosorbide dinitrate , chemistry , medicine , calcium , calcium channel , heart rate , antagonist , blood pressure , receptor
Summary— It is rather the rate of the vasodilator effect than its magnitude which determines the triggering of reflex tachycardia associated with dihydropyridine calcium antagonists (DHP‐CA). We therefore compared the rate of the vasodilator effects of a series of CA (both DHP and non‐DHP) in rat isolated mesenteric artery preparations (size 256 ± 3 μm, length 2 mm) from male Wistar rats (weighing 300–350 g) in an isolated wire myograph according to Mulvany and Halpern [12]. The mean force of the KCl‐induced contraction amounted to 2.3 ± 0.1 mN/mm. Potency (given as IC 50 ‐values), differential time course of action and recovery of the contractile response of the vessels after wash‐out were established. These three parameters adhere to the following sequences; (1. potency) S,S‐barnidipine > (S)‐lercanidipine > barnidipine HCl > amlodipine > nifedipine, lacidipine > (R)‐lercanidipine > verapamil, mibefradil; (2. differential time course) lacidipine, amlodipine > (S)‐ and (R)‐lercanidipine. S,S‐barnidipine, barnidipine HCl > mibefradil, verapamil, nifedipine; (3. recovery) nifedipine > verapamil, S,S‐barnidipine, amlodipine > barnidipine, lacidipine > mibefradil, (R)‐lercanidipine > (S)‐lercanidipine. In conclusion, S,S‐barnidipine proved to be the most potent vasodilator agent; interestingly, barnidipine was 20 times less potent when applied as a racemic mixture. A slow onset of action in DHP is a very important mechanism in preventing reflex tachycardia. For non‐DHP (verapamil, mibefradil) reflex tachycardia probably is prevented by a direct effect on the conductive tissue in the myocardium.