Calcium channel blockers development

These drugs were developed as coronary vasodilating agents and were used for that purpose for some time, until it was discovered that they inhibit the contractile effect of calcium on smooth musculature and cardiac muscle, and that they affect calcium channels on the cell surface that permit calcium ions to enter. At first, they were called calcium antagonists however, later on this class of compounds was given the preferred name of calcium channel blockers. 

A significant body of evidence suggests that the calcium channel blockers may interfere with platelet aggregation in vitro and prevent or attenuate the development of atheromatous lesions in animals. Clinical studies have not established their role in human blood clotting and atherosclerosis. 

Some issues, however, have developed fairly recently regarding the safety of these drugs in treating hypertension. Several studies noted that use of certain calcium channel blockers (i.e., the short-acting form of nifedipine) was associated with an increased risk of myocardial infarction when these drugs were adminis-... 

Procardia XL, which is marketed by Pfizer, is a billion-dollar product employing Push-Pull technology. The preparation contains the calcium channel blocker nifedipine.40 A full list of marketed products developed by ALZA Corporation is shown in Table 7.4. 

Two isomers of teludipine (54), R-enantiomer (GR66234A) and L-cn-antiomer (GR66235 A) which were originally developed as a new lipophilic calcium channel blocker by Glaxo were evaluated for daunorubicin resistance reversal activity and found to be more effective than verapamil. Additionally, the difference in activity was also found on different cells. Verapamil and the enantiomers of teludipine are more active in ARNII cells than in MCF 7/R cells. There were no apparent differences in cellular daunorubicin accumulation between ARNII and MCF 7/R following exposure to teludipine and no differences in intracellular daunorubicin distribution in the presence of either MDR reversing agent were observed [97]. 

Fratantoni SA, Weisz G, Pai dal AM, Reisin RC, Uchitel OD (2000) Amyoti ophic lateral sclerosis IgG-deated neuromuscular junc-dons develop sensidvity to L-type calcium channel blocker. Muscle Nerve 23 543-550. 

Adverse respiratory effects are uncommon with calcium channel blockers. However, three cases of acute broncho-spasm accompanied by urticaria and pruritus have been reported in patients taking verapamil (51), and a patient with Duchenne-type muscular dystrophy developed respiratory failure during intravenous verapamil therapy for supraventricular tachycardia (52). Recurrent exarcer-bations of asthma occurred in a 66-year-old lady with hypertension and bronchial asthma given modified-release verapamil (53). 

Calcium channel blockers can cause parkinsonism. Of 32 patients with this complication, only three had made a full recovery 18 months after withdrawal patients under 73 years of age tended to have a better prognosis (57). It is not known if these patients would have developed parkinsonism in any case, and whether the drugs merely act as precipitants. 

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