Nicardipine, calcium channel blocking

The effects of the prototypical calcium channel blockers are seen most prominently in the cardiovascular system (Table 19.1), although calcium channels are widely distributed among excitable cells. The following calcium channel-blocking drugs are clinically the most widely used compounds in this very extensive class of pharmacological agents amlodipine, diltiazem, isradipine, nifedipine, nicardipine, nimodipine, and verapamil. 

Some members of calcium channel blockers, such as nicardipine (40) and ni-modipine (41), were identified as potent MDR antagonists. This early work stressed the lack of correlation between the calcium channel blocking and anti-MDR potencies [75]. It has been reported that DHPs bind to a site that is allosterically coupled to the receptor site which binds anticancer agents and other MDR reversal agents [76,77]. DHPs are well recognized as privileged structure for their multi-receptor affinity [78,79]. 

Calcium channel blocking drugs which are currently licensed for use in the United Kingdom are presented in Table 7.5, nicardipine being the most recent addition to the list. To date, all the indications are of a cardiovascular nature and, indeed, the calcium channel blocking drugs have now become established as an important group of cardiovascular medicines. 

Nicardipine is a calcium-channel-blocking agent that inhibits movement of calcium ions across cell membrane in systemic and coronary vascular smooth muscle and myocardium. It is indicated in the treatment of chronic stable (effort-associated) angina (immediate-release capsules) management of hypertension (immediate and sustained-release capsules and by IV when oral therapy is not feasible or desirable). 

The calcium channel blockers generally are considered seconder third-line options for preventive treatment when other drugs with established clinical benefit are ineffective or contraindicated. Verapamil is the most widely used calcium chaimel blocker for preventive treatment, but it provided only modest benefit in decreasing the frequency of attacks in two placebo-controlled studies." The therapeutic effect of verapamil may not be noted for up to 8 weeks after initiation of therapy. Side effects of verapamil may include constipation, hypotension, bradycardia, atrioventricular block, and exacerbation of congestive heart failure. Evaluations of nifedipine, nimodipine, diltiazem, and nicardipine have yielded equivocal results. ... 

Pharmaceutical chemists, too, have evinced a keen interest in DHA chemistry, particularly the 4-aryldihydropyridines, which exhibit powerful vasodilating activities via the blocking of calcium channels and modifying movement of Ca2+ into and within the cell. The explosion in activity in this area of heterocyclic synthesis has produced an exponential growth in patent applications and papers and has led to the marketing of a new drug, nifedipine (4).6 Other active 4-aryldihydropyridine derivatives, such as nimodipine and nicardipine (cerebral vasodilators) and nitrendipine (antihypertensive), are presently under clinical trials.7 An excellent list of other practical applications of dihydropyridines has been collected by Kuthan and Kurfiirst.2... 

Calcium channel blockers, also known as calcium antagonists, are a class of hypertension drugs that inhibit the influx of calcium ions through the cell membrane. A decrease in calcium ions results in less contraction of the cardiac and vascular muscles. There is an increase in the diameter of the arteries. This vasodilatation results in a lowering of the blood pressure. Despite their name, calcium channel blockers do not plug the hole and physically block the calcium ion channel. Rather, they bind to specific receptor sites [30]. Examples of calcium channel blockers are nifedipine (Procardia , Pfizer), nicardipine hydrochloride, amlodipine besylate sulfonate (Norvasc , Pfizer) and verapamil hydrochloride (Calan , Pfizer). Verapamil has a chiral carbon but is administered as a racemic mixture. 

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