Nimodipine, 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. 

The calcium channel blocking drugs may prove to be very useful in the treatment of patients following acute stroke. In particular, nimodipine has been found to have selective actions on cerebral vascular smooth muscle without affecting systemic arterial pressure [16]. After intravenous administration, nimodipine increases hemispheric cerebral blood flow in patients with acute ischaemic stroke [235]. A placebo-controlled double-blind trial has shown that nimodipine significantly decreases the occurrence of severe neurologic deficits from spasm alone in patients who have had subarachnoid haemorrhage [236],... 

Calcium Channel Blockers. The calcium channel blockers work by blocking the influx of calcium, an excitatory ion, into the cell. The first calcium channel blocker, verapamil (Calan), was introduced in the 1960s. Others, including diltiazem, nifedipine, and nimodipine, are now available. The calcium channel blockers have been used to treat a variety of medical conditions including high blood pressure, cardiac pain (angina) and arrhythmias, migraines, seizure disorders, and premature labor. 

Four categories of calcium channel blockers can be defined based on their chemical structures and actions diphenylalkylamines, benzothiazepines, dihydropyridines, and bepridil. Both diphenylalkylamines (verapamil) and benzothiazepines (diltiazem) exhibit effects on both cardiac and vascular tissue. With specificity for the heart tissue, these two types of calcium channel blockers can slow conduction through the AV node and are useful in treating arrhythmias. The dihydropyridines (nifedipine is the prototypical agent) are more potent peripheral and coronary artery vasodilators. They do not affect cardiac conduction, but can dilate coronary arteries. They are particularly useful as antianginal agents. Bepridil is unique in that it blocks both fast sodium channels and calcium channels in the heart. All calcium channel blockers, except nimodipine and bepridil, are effective in treating HTN. 

The CALCIUM-CHANNEL BLOCKERS, e.g. diltiazem, nimodipine and verapamil, act to block a subset of voltage-sensitive calcium channels, so reducing Ca -influx into smooth muscle cells. The potassium-channel activators. e.g. cromakalim, diazoxide, minoxidil, nicorandil and pinacidil, are thought to work by opening a subset of K -channels which leads to membrane stabilization. 

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. ... 

Calcium channel antagonists enhance vasodilation by blocking L-type Ca2+ channels in cardiac and vascular tissues. They are particularly effective for elderly and African American patients. Drugs considered are verapamil, diltiazem, nifedipine, and nimodipine. 

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... 

Fig. 3.1-8 The activity of an exogenenous nimodipine, the endogenous, wild-type L-type calcium channel was dissected using channel (blue) is blocked and the activity of a mutation that effects nimodipine the mutant channel (green) is revealed,...

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