Flunarizine A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Use

Abstract

Flunarizine is a 'selective' calcium entry blocker with a similar chemical structure and pharmacological profile to the related compound, cinnarizine. However, in contrast to cinnarizine it has a long plasma half-life and need only be given once a day. The majority of therapeutic trials in the prophylaxis of migraine, occlusive peripheral vascular disease and vertigo of central or peripheral origin have been placebo-controlled, and have shown that the drug produces significantly greater beneficial effects than placebo as evaluated by subjective and objective criteria. A small number of comparative studies have shown flunarizine to be at least as effective as pizotifen in migraine prophylaxis, and in a longer term study as effective as cinnarizine in vertigo of central origin. However, it has not been compared with other drugs which may be useful in these areas, such as methysergide in migraine prophylaxis, some antihistamines or phenothiazines in vertigo, or (understandably at this stage of its evolution) with surgical revascularisation in severe occlusive peripheral vascular disease. In preliminary placebo-controlled studies there was some evidence that flunarizine may improve impaired cognitive function in patients with cerebrovascular disorders, but such findings need further confirmation in additional carefully conducted studies. With a very long half-life, flunarizine may be given once daily; and drowsiness, the main side effect, can be minimised by taking the daily dose in the evening. Thus, it appears that flunarizine will offer a useful alternative in some therapeutic areas that can be difficult to manage with previously available therapy. However, a definitive statement on its relative place in therapy of such conditions must await a few well-controlled comparative studies.

Flunarizine inhibits endothelium‐dependent hypoxic facilitation in canine coronary arteries through an action on vascular smooth muscle

“…The present experiments were designed to determine whether the inhibition of the hypoxic facilitation by these drugs is due to an action on the endothelium, on the vascular smooth muscle, or on both. To do so we used a layered preparation which allowed treatment of the endothelium and the vascular smooth muscle separately and selected flunarizine, a difluoro derivative of piperazine which inhibits Ca2 '-entry (Van Nueten & Janssen, 1973;Holmes et al, 1984;Borgers et al, 1984) and has a longer duration of action than diltiazem, nifedipine, and verapamil (Van Nueten et al, 1978;Godfraind & Dieu, 1981). This allowed us to treat the endothelium and the vascular smooth muscle separately.…”

Three-dimensional hydrogen-bonded framework structures in flunarizinium nicotinate and flunarizinediium bis(4-toluenesulfonate) dihydrate

“…Its pharmacodynamic and pharmacokinetic properties and its therapeutic use have been reviewed (Holmes et al, 1984). Brief reports on the structures of several salts derived from flunarizine Shivaprakash et al, 2014) and from substituted piperazine derivatives closely related to flunarizine Kavitha, Yildirim et al, 2013) have been published recently, and we report here the molecular and supramolecular structures of flunarizinium nicotinate, (I) (Fig.…”

Termination of a tachyarrhythmia by flunarizine is not a specific marker for a triggered mechanism

“…Flunarizine, a difluorinated piperazine derivative, has been shown to block L-type and T-type calcium channels, and is thought to block accumulation of intracellular calcium selectively during calcium overload (1)(2)(3). However, the exact mechanism of its action remains unclear.…”

“…Flunarizine has undergone clinical trials in several therapeutic areas, including migraine headache prophylaxis, peripheral vascular disease, and vertigo (1). In addition, in animal models, flunarizine has been shown to abolish ouabain-and catecholamine-induced delayed afterdepolarizations in vitro in isolated rat cardiac myocytes (11), and to terminate triggered ventricular arrhythmias in a ouabain-induced ventricular tachycardia model in the intact canine heart (12).…”