Calcium entry blockers

While the molecular identity of the capacitative Ca2+ entry channel is not known, a candidate is a homolog of the Drosophila mutant trp. This photoreceptor mutant is incapable of maintaining a sustained photoreceptor potential. This phenotype could be mimicked by the calcium entry blocker lanthanum, and it was suggested that the related defect is a failure of Ca2+ entry. 

When coronary vasospasm occurs, the balance between oxygen supply and demand can be restored by relieving the spasm, thereby restoring normal coronary blood flow. Acute vasospasm has been successfully aborted through the use of nitroglycerin. In contrast, calcium entry blockers and long-acting nitrates have proved effective in the chronic therapy of coronary vasospasm. 

Propranolol and nadolol also have been used successfully in combination with certain calcium entry blockers, particularly nifedipine, for the treatment of secondary angina. Caution should be used, however, when combining a p-blocker and a calcium channel blocker, such as verapamil or diltiazem, since the negative inotropic and chronotropic effects of this combination may lead to severe bradycardia, arteriovenous nodal block, or decompensated congestive heart failure. 

Determinant Nitrates P-Receptor Blockers Calcium Entry Blockers... 

The calcium entry blockers or calcium channel blockers are a group of orally active drugs that have been approved for use in the treatment of vasospastic and ef-... 

The concept of calcium antagonism as a specific mechanism of drug action was pioneered by Albrecht Fleckenstein and his colleagues, who observed that verapamil and subsequently other drugs of this class mimicked in reversible fashion the effects of Ca++ withdrawal on cardiac excitability. These drugs inhibited the Ca" + component of the ionic currents carried in the cardiac action potential. Because of this activity, these drugs are also referred to as slow channel blockers, calcium channel antagonists, and calcium entry blockers. 

Traditional long-term anti-ischaemic triple therapy for coronary artery disease consists of a long-acting nitrate, p-adrenoceptor antagonist and a calcium-entry blocker. Most of these agents are also used for the treatment of hypertension. 

Class IV drugs are calcium-entry blockers of the phenylalkylamine (verapamil) and benzothiazepine (diltiazem) type. They slow atrioventricular conduction, and are used to treat supraventricular and sinus tachycardia. 

Therapeutic Function Antihistaminic, Antiallergic, Calcium entry blocker... 

Therapeutic Function Calcium entry blocker, Antihypertensive... 

Hazel SJ, Gillespie CM, Moore RJ et al. (1994) Enhanced body growth in uremic rats treated with IGF-I and growth hormone in combination. Kidney Int 46 58-68 Jarusiripipat C, Chan L, Shapiro JI, Schrier RW (1992) Effect of long-acting calcium entry blocker (anipamil) on blood pressure, renal function and survival of uremic rats. J Pharmacol Exp Ther 260 243-247... 

Calcium entry blockers, e.g. verapamil, flimarizine, may provide benefit. 

Bova S, Cima L, Golovina V, Luciani S, and Cargnelli G (2001) Norbormide A calcium entry blocker with selective vasoconstrictor activity in rat peripheral arteries. Cardiovascular Drug Reviews 19(3) 226-233. 

Corelli F, Manetti F, Tafi A, Campiani G, Nacci V, Botta M. Diltiazem-like calcium entry blockers A hypothesis of the receptor-binding site based on a comparative molecular field analysis model. J Med Chem 1997 40 125-31. 

J.C. Stoclet, C. Lugnier, A. Follenius, J.M. Scheftel and D. Gerard, in Calcium Entry Blockers and Tissue Protection, eds. T. Godfraind, P.M. Vanhoutte, S. Govoni and R. Paoletti (Raven Press, New York, 1985) pp. 31-40. 

Gl. Garay, G. L., Annesley, P., and Burnett, M., Prevention of experimental liver injury in rats by nicardipine, a calcium entry blocker. Gastroenterology 86, 1319 (1984). 

A perfluoroisopentylpyran was tested as a vehicle for administering therapeutic drugs (83EUP91313). 2-Amino-3-cyano-4//-pyran 295 (R1 = Me,R2 = 3-02NC6H4,R3 = H,X = C02Et) and its 3,5-diester were tested as antibodies to dihydropyridine calcium entry blockers (86BP4479). Complex 4/7-pyran 3,5-diester 53c did not exhibit antihypertensive activity... 

Slow Calcium Channel Blockers (SCCBs), which are also referred to as calcium entry blockers and even, erroneously, as calcium antagonists, are a number of marketed drugs, several of which have no chemical relationship to the others. They will be discussed in some detail with the anti-anginal drugs (see later). At this point, suffice it to state that their antihypertensive effect is due to their ability to modulate the influx of Ca2+ across the cell membrane of the arterial smooth muscle. This will reduce Ca2+-promoted activation of the cells contractile proteins, leading to vasodilation. 

Unlike skeletal muscles, which contain endogenons stores of calcium ions, both cardiac muscle and vascnlar smooth muscle require extracellular calcium for contractile function. Therefore, cardiac muscle and vascnlar smooth muscle are subject to regulation by calcium antagonists or calcium entry blockers (Figure 103 and Table 21), which are used in the treatment of hypertension, Raynand s disease, Prinzmetal s angina, and migraine syndromes. 

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 ... 

There are also nonselective calcium-entry blockers that act at similar concentrations on both calcium channels and fast sodium channels. These agents consist of bencyclane, bepridil, caroverine, etafenone, fendihne, lidoflazine, per-hexiline, prenylamine, proadifen, terodiline, and tiapamil. 

Heart failure is associated with changes in the intracellular calcium levels. The rationale for using calcium-entry blockers in preventing the secondary comphcations of myocardial infarction stems from the fact that these agents reduce systemic vascular resistance, afterload, myocardial contrac-tihty, blood pressure, and oxygen consumption. However, despite these effects, the efficacy of calcium-entry blockers in preventing the secondary comphcations of myocardial infarction or their usefulness in the context of cerebrovascular diseases such as aneurysmal subarachnoid hemorrhage needs to be established. 

Beta-adrenergic blocking agents are effective for the prophylactic therapy of exertional angina pectoris by reducing heart rate and the force of myocardial contraction. However, verapamil, nifedipine, and diltiazem are also effective for the prophylactic treatment of stable exertional angina. The combination therapy with beta-blockers and calcium-entry blockers is well tolerated, effective, and safe. 

Among the various types of calcium-entry blockers, flunarizine has proved to be the most effective in the prophylaxis of migraine. It has also been shown to be beneficial in protecting brain cells against hypoxia and in preventing the constriction of cerebrovascular smooth-muscle cells. Moreover, it has been shown to be effective in the treatment of epilepsy and hemiplegia. 

Calcium-entry blockers may induce extrapyramidal symptoms and aggravate parkinsonism. 

Drug Interactions and Calcium-Entry Blockers The following are some of the drug interactions seen with either specific calcium-entry blockers or these agents in general ... 

Calcium-entry blockers potentiate the hypotensive effects of prazocin. 

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