Antihypertensive mechanism of action and binding sites of nitrendipine.
Members of the 1,4 dihydropyridine category of the calcium channel antagonists, including nitrendipine, have defined structure-activity relations that involve both their specificity and their sites of action. Other categories of calcium channel antagonists, such as D600, verapamil and diltiazem, differ from the 1,4 dihydropyridines in a number of aspects, including lower potency. All of the calcium channel antagonists share the ability to inhibit calcium currents passing through a voltage-dependent calcium channel. The 1,4 dihydropyridines are relatively selective for vascular smooth muscle. Because of this selectivity, nitrendipine has potent action as an antihypertensive drug. Although biochemical radioligand binding studies have shown that the same type of high affinity binding sites occur in cardiac muscle as in vascular smooth muscle, it is not fully established why the 1,4 dihydropyridines are not as potent in cardiac as in vascular muscle. Other members of the very large 1,4 dihydropyridine category of calcium channel antagonists include nifedipine, nimodipine and nisoldipine. The 1,4 dihydropyridines also include recently discovered calcium channel activators, including the compound Bay K 8644. These calcium channel activators are diametrically opposed in properties to nifedipine and nitrendipine. Thus, this single structural category of compounds has a complete spectrum of pharmacologic activity at Ca++ channels, from turning on to turning off.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels; D006321:Heart / Q000187:drug effects; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D009568:Nitrendipine / Q000378:metabolism / Q000494:pharmacology*; D009928:Organ Specificity; D011869:Radioligand Assay; D011978:Receptors, Nicotinic; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007473:Ion Channels; D011978:Receptors, Nicotinic; D009568:Nitrendipine; D002118:Calcium