Calcium channel blockers phenylalkylamines

Calcium is involved in the contraction of cardiac and vascular smooth muscle cells, and in the auto-maticity of cardiac pacemaker cells. Actions of calcium channel blockers on vascular smooth muscle cells are described with the main account of these drugs in Chapter 23. Although the three classes of calcium channel blocker have similar effects on vascular smooth muscle in the arterial tree, their cardiac actions differ. The phenylalkylamine, verapamil, depresses myocardial contraction more than the others, and both verapamil and the benzothiazepine, diltiazem, slow conduction in the SA and AV nodes. 

Verapamil is a phenylalkylamine calcium channel blocker, with actions mainly on the heart. 

Goll A, Glossmann H, Mannhold R. Correlation between the negative inotropic potency and binding parameters of 1,4-dihydropyridine and phenylalkylamine calcium channel blockers in cat heart. Naunyn Schmiedebergs Arch Pharmacol 1986 334 303-12. 

Cayl channels (L-type) are targets of calcium-channel blockers or calcium antagonists which decrease the influx of Ca + in cardiac and smooth muscle vascular cells dihy-dropyridines (nifedipine and analogs), phenylalkylamines (verapamil) and benzothiazepines (diltiazem), widely used as antihypertensive, antianginal and antiarrhythmic drugs. Cayl openers, like Bay K 8644, have been synthesized but have not found any therapeutic interest. 

There are approximately a dozen calcium channel antagonists marketed in the United States for the treatment of hypertension, certain dysrhythmias, and some forms of angina (see Chaps. 13,15, and 17). The calcium channel blockers are classified by their chemical structure as phenylalkylamines (e.g., verapamil), benzothiapines (e.g., diltiazem), and dihydropyridines (e.g., amlodipine, felodipine, nicardipine, and nifedipine). Several of these agents, namely, diltiazem, nicardipine, nifedipine, and verapamil, are formulated as sustained-release oral dosage forms or have a slow onset of action and longer half-life (e.g., amlodipine " ), allowing once-daily administration. 

L-type or high-voltage-activated calcium channels carry the majority of the calcium inward current in smooth muscle cells. They start to activate at a high membrane potential (around -30 mV) with a maximum at slightly positive membrane potentials (around -f-10 mV), have a large conductance (20-25 pS with 110 mM Ba2+ as charge carrier), inactivate slowly, and are readily and specifically blocked by the classic organic calcium channel blockers nifedipine (a 1,4-dihydro-pyridine), verapamil (a phenylalkylamine), and dil-tiazem (a benzothiazepine) (see Hofmann etah, 1994). 

Calcium-entry blockers include those agents that are selective for slow calcium channels in the myocardium (slow channel blockers) and consist of the following categories of substances benzothiazepines (diltiazem and dihydropy-ridines)—nifedipine, nicardipine, niludipine, nimodipine, nisoldipine, nitrendipine, ryosidine, amlodipine, azodipine, dazodipine, felodipine, flordipine, iodipine, isradipine, mesu-dipine, oxodipine, and riodipine and, phenylalkylamines— verapamil, gallopamil, anipamil, desmethoxyverapamil, emopamil, falipamil, and ronipamil. 

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