Calcium antagonistic activity

OE136 Rauwald, H. W., O. Brehm, and K. P. Odenthal. Screening of nine vasoactive medicinal plants for their possible calcium antagonistic activity. Strategy of selection and isolation for the active principles of Olea europaea and Pseucedanum ostrithium. Phytother Res 1994 8(3) 135-140. 

AF1057>. There was a difference in the calcium antagonistic activities between the enantiomers of monatepil maleate 267 but not in their cti-adrenergic receptor blocking activity. 

Isradipine (Fig. 7.5) is a further nifedipine analogue, which has been used in the treatment of hypertension either alone or in combination with diuretics. Isradipine possesses high calcium antagonist activity, which results in a peripheral vasodilatation without any detrimental effect on cardiac conduction. Its oral bioavailability is 90-95% of the administered dose, but the hepatic first-pass effect reduces this to 15-24%. Isradipine was shown to possess anti-atherosclerotic activity in a number of experimental models, but clinical studies (MIDAS) failed to confirm these findings in patients. 

Manidipine (Fig. 7.11) is a nifedipine analogue which shows a potent and selective calcium antagonist activity that translates into a potent antihypertensive and coronary vasodilatory activity. Manidipine shows some selectivity towards the renal vasculature, making it particularly useful for the treatment of renovascular hypertension. 

The substitution pattern of the 4-aromatic residue is also important for the activity, the ortho-substitution being the best one in terms of potency and selectivity. A Hansch analysis on a series of ortho-derivatives has shown a significant correlation between calcium antagonist activity and steric hindrance of the substituent, while no relationship was found for either electronic or lipophilic parameters [3]. The best SAR correlation was obtained when the B1 steric parameter (the Verloop parameter) was introduced into the analysis [4]. The calcium channel-blocking activity increases as B1 increases, which probably indicates that steric hindrance in the ortho-position is required to fix the dihydropyridine structure into a favorable conformation in which the aromatic group is approximately perpendicular to the dihydropyridine ring (Fig. 7.12). 

In contrast, amiodarone and sotalol are effective in most supraventricular and ventricular tachycardias. Amiodarone displays electrophysiologic characteristics consistent with each type of antiarrhythmic drug, ft is a sodium channel blocker with relatively fast on-off kinetics, has nonselec-tive j8-blocking actions, blocks potassium channels, and has slight calcium antagonist activity. The impressive effectiveness and low proarrhythmic potential of amiodarone have challenged the notion that selective ion channel blockade is preferable. Sotalol is a potent inhibitor of outward... 

The interaction energies between an arginine side chain and the aromatic ring close to the chiral center of verapamil analogs could be correlated with their calcium antagonistic activities (n = 10 r = 0.973 s = 0.095) [899]. 

Constit. of M. fargesii and P. wightii. Possesses calcium antagonistic activity. Viscous oil. [a]j —196 (c, 1 in CHCI3). 

Taylor, B. A., Duthie, H. L., Luscombe, D. K. 1985. Calcium antagonist activity of menthol on gastrointestinal smooth muscle. Br. J. Clin. Pharm. 20 293-294. 

Shoji, N., A. Umeyama, Y. Asakawa, T. Takeout, K. Nocoton, andY. Ohizumi, 1984. Structure determination of nootkatol, a new sesquiterpene isolated form Alpinia oxyphylla Miquel possessing calcium antagonist activity, 73 843-844. 

Dar A, Channa S (1999) Calcium antagonistic activity of Bacopa monniera on vascular and intestinal smooth muscles of rabbit and guinea-pig. J Ethnopharmacol 66 167-174... 

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