The newer
dihydropyridine calcium antagonists are structurally related to
nifedipine, but may provide greater vascular selectivity and wider clinical utility. Five new
dihydropyridines-
nisoldipine,
nicardipine,
nimodipine,
felodipine and
nitrendipine-are reviewed with regard to their preclinical pharmacology, haemodynamic effects and clinical indications.
Nisoldipine is a potent arterial
vasodilator with minimal electrophysiological and negative inotropic effects. Although data are still preliminary, the
drug has shown some efficacy in both exertional angina and
essential hypertension. The dosing interval is not yet clearly established, but may be twice daily. Utility in
congestive heart failure awaits confirmation, but preliminary studies are promising.
Nicardipine is an especially potent peripheral, cerebral and coronary arterial
vasodilator that causes 10-fold less myocardial depression in animals than
nifedipine, and may provide important cardioprotective effects during ischaemia. Human haemodynamic studies have confirmed
nicardipine's lack of negative inotropism, its ability to reduce coronary and peripheral vascular resistance, and its lack of effect on cardiac conduction. Several controlled trials have documented its efficacy in exertional angina, vasospastic angina, and
essential hypertension.
Nicardipine's potential as an antiatherosclerotic agent is currently under investigation.
Nimodipine is undergoing a unique clinical development programme aimed at
cerebrovascular disorders. In almost all species,
nimodipine selectively increases cerebral blood flow and reverses
cerebral artery spasm without altering cerebral oxidative metabolism or systemic blood pressure. In humans, a large, double-blind, placebo-controlled trial in subarachnoid haemorrhage showed that
nimodipine significantly reduced the severity of neurological deficits associated with delayed
cerebral vasospasm. Several uncontrolled trials with larger numbers of patients support these results.
Nimodipine has also proved useful in reducing
cerebral artery spasm during intracranial surgery, and in the prophylactic treatment of
migraine headaches. A preliminary study of
nimodipine in
acute stroke showed promising results in limiting neurological disability.
Felodipine is a very potent systemic arterial
vasodilator with negligible
myocardial depressant activity. It is also a renal artery
vasodilator. Unlike the other new
dihydropyridines,
felodipine prolongs the A-H interval on electrophysiological testing, but only to about 50% of that observed with
verapamil.
Felodipine is undergoing clinical trials in
essential hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)