Pharmacodynamic profiles of different calcium channel blockers.
The cardiovascular effects of different calcium channel blockers (CCB), exemplified by nifedipine, verapamil and diltiazem, are not identical. Some of these differences in effect may be due to the different CCBs interacting with different calcium channel subtypes in the tissues, and/or that the drug-receptor sites are separate. The drugs also have different abilities to activate the sympathetic nervous system, nifedipine increasing and diltiazem decreasing the baroreflex sensitivity. Verapamil, but not nifedipine and diltiazem, has a postjunctional alpha-adrenoceptor blocking effect, and can also increase the release of noradrenaline from adrenergic nerves by blocking pre-junctional alpha-adrenoceptors. In addition, verapamil may have a reserpine-like action on sympathetic nerves. The vasodilator actions of CCBs are not uniform, but seem to vary between species, different vascular regions, and different agents. Mechanisms other than blockade of influx of calcium from the extracellular medium have been suggested to explain these differences, including inhibition of intracellular calcium release, blockade of postjunctional alpha-adrenoceptors, interaction with calmodulin, inhibition of cyclic AMP phosphodiesterase, stimulation of Na+-, K+-activated ATPase, stimulation of a calcium pump, and a direct interaction with the contractile proteins. The heterogeneity in pharmacodynamic profile characterizing the CCBs is conspicuous, and may be of importance when selecting agents for the treatment of various cardiovascular and non-cardiovascular disorders.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000317:Adrenergic alpha-Antagonists; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D002147:Calmodulin / Q000378:metabolism; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D003285:Contractile Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D002147:Calmodulin; D003285:Contractile Proteins; D007473:Ion Channels; D011955:Receptors, Drug; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium