The antivasoconstrictor activity of the drugs cinnarizine and flunarizine is considered in relation to their inhibitory action on calcium ion flux mechanisms. Their clinical efficacy in peripheral vascular disease is reviewed, and the possible mode of action of the two drugs is discussed in relation to their described pharmacologic effects.
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References
1.
Ringer, S.: A further contribution regarding the influence of different constituents of the blood on the contraction of the heart. J. Physiol., 4: 29, 1883.
2.
Heilbrunn, L.V. , Wiercinski, F.J.: The action of various cations on muscle protoplasm. J. Cell. Comp. Physiol., 29: 15, 1947.
3.
Perry, S.V.: Calcium ions and the function of the contractile proteins of muscle. Biochem. Soc. Symp., London, 39: 115, 1974.
4.
Edman, K.A.P. , Schild, H.O.: The need for calcium in the contractile responses induced by acetylcholine and potassium in the rat uterus. J. Physiol., 161: 424, 1962.
5.
Godfraind, T. , Kaba, A.: The role of calcium in the action of drugs on vascular smooth muscle. Arch. Int. Pharmacodyn. Ther.196: 35, 1972 (Suppl.).
6.
Godfraind, T. , Kaba, A., Rojas, R.: Inhibition by cinnarizine of calcium channels opening in depolarized smooth muscle. Br. J. Pharmacol., 49: 164P, 1973.
7.
Zolov, B.: Clinical evaluation of cinnarizine (Mitronal) in various allergic disorders . Ann. Allergy, 19: 1290, 1961.
8.
Trumbull, R. , Chinn, H.I., Maag, C.H., et al.: Effects of certain drugs on the incidence of seasickness. Clin. Pharmacol. Ther., 1: 280, 1960.
9.
Philipszoon, A.J.: Influence of cinnarizine on the labyrinth and on vertigo. Clin. Pharmacol. Ther., 3: 184, 1962.
10.
Van Nueten, J.M.: Comparative bioassay of vasoactive drugs using isolated perfused rabbit arteries. Eur. J. Pharmacol. , 6: 286, 1969.
11.
Adriaensen, H.: The treatment of intermittent claudication . Clin. Trials J., 6: 191, 1969.
12.
Van Nueten, J.M. : Study of the action of cinnarizine on the vasoconstrictor effects of vasoactive agents in perfused peripheral arteries. Janssen Pharmaceutica (Beerse, Belgium) Internal Report No. 6267, 1968.
13.
Godfraind, T., Morel, N.: An upper limit to the number of calcium ions in smooth muscle as estimated with cinnarizine. Eur. J. Pharmacol. , 41: 245, 1977.
14.
Di Perri, T. , Forconi, S., Guerrini, M., et al.: Action of cinnarizine on the hyperviscosity of blood in patients with peripheral obliterative arterial disease. Proc. R. Soc. Med., 70: 25, 1977 (Suppl. 8).
15.
Van Nueten, J.M., Janssen, P.A.J.: Comparative study of the effects of flunarizine and cinnarizine on smooth muscles and cardiac tissues. Arch. Int. Pharmacodyn. Ther., 204: 37, 1973.
16.
Pfeffer, G. : The effect of cinnarizine after 6-8 weeks of treatment in patients with arterial and venous peripheral circulation disorders . Arztliche Praxis, 22: 493, 1968.
17.
Verdonk, G.: Cinnarizine in the treatment of peripheral vascular arteriosclerotic disorders: Clinical and electrothermometric report. Janssen Pharmaceutica (Beerse, Belgium) Internal Report No. 2636, 1968.
18.
Joos, F.: Invloed van cinnarizine bij de behandeling van gestabiliseerde claudicatio intermittens. Folia St. Jan., 2: 176, 1968.
19.
Put, T.: The therapeutic value of cinnarizine in cervico-brachial and ischial syndromes . Arzneim. Forsch. Drug Res., 19: 1868, 1969 .
20.
Schuermans, V., Boermans, A., Geivers, H., Cinnarizine in peripheral vascular insufficiency . Arzneim. Forsch. Drug Res., 21: 1541, 1971 .
21.
Verhaegen, H., Roels, V., Adriaensen, H., et al.: The arteriolar effects of cinnarizine and flunarizine. Multitechnical investigations in normal volunteers and in patients with occlusive disease of the extremities secondary to arteriosclerosis . Angiology, 25: 261, 1974.
22.
Emanuel, M.B. , Will, J.A.: Cinnarizine in the treatment of peripheral vascular disease: Mechanisms related to its clinical action. Proc. R. Soc. Med., 70: 7, 1977 (Suppl. 8).
23.
Brugmans, J. , Jageneau, A.H.M., Hörig, C., et al.: Modern techniques of venous occlusion plethysmography in the assessment of peripheral vascular disease. Proc. R. Soc. Med., 70: 1, 1977 (Suppl. 8).
24.
Jageneau, A.H.M. , Haag, F.: Flunarizin bei Patienten mit Durchblutangsstörungen der unteren Extremitäten. Med. Welt., Bb 28/ Heft 23: 1050, 1977.
25.
Schetz, J., Bostoen, H., Clement, D., et al.: Flunarizine in chronic obstructive peripheral arterial disease: A placebo-controlled, double-blind, randomized multicentre trial. Curr. Ther. Res., 23: 121, 1977.
26.
Domschky, K. , Nelson, M., Dammhayn, B., et al.: Flunarizin bei Patienten mit zerebraler und peripherer Mangelddurchblutung. Med. Welt., Bd 28/Heft 23: 1062, 1977.
27.
Oosterveld, W.J.: Pilot evaluation of flunarizine (R 14950) in vertigo—a double-blind trial. Can. J. Otolaryngol. , 3: 284, 1974.
28.
De Clerck, F., De Cree, J., Brugmans, J., et al.: Reduction by flunarizine of the increase of blood viscosity after ischemic forearm occlusion. Arch. Int. Pharmacodyn. Ther., 230: 321, 1977.
29.
Godfraind, T., Kaba, A.: Blockade or reversal of the contraction induced by calcium and adrenaline in depolarized arterial smooth muscle. Br. J. Pharmacol., 36: 549, 1969.
30.
Van Nueten, J.M., Van Beek, J., Janssen, P.A.J.: Effect of flunarizine on calcium-induced responses of peripheral vascular smooth muscle. Arch. Int. Pharmacodyn. Ther., 232: 42, 1978.
31.
Weed, R.I., La Celle, P.L., Merrill, E.W.: Metabolic dependence of red cell deformability. J. Clin. Invest. , 48: 795, 1969.
32.
Van Nueten, J.M., Janssen P.A.J.: Effect of cinnarizine on peripheral circulation in dogs. Eur. J. Pharmacol., 17: 103, 1972.
33.
Lecomte, J. , Cession-Fossion, A., Cession, G.: Action de quelques antihistaminiques de synthese sur les effets vasopresseurs de la noradrenaline chez le rat. Comptes Rendus des Seances de la Societé de Biologie et de Ses Filiales, 159: 515, 1965.
34.
Dormandy, J.A. , Hoare, E., Colley, J., et al.: Clinical, haemodynamic, rheological and biochemical findings in 126 patients with intermittent claudication. Br. Med. J., 4: 576, 1973.
Barnes, A.J., Locke, P., Scudder, P.R., et al.: Is hyperviscosity a treatable component of diabetic microcirculatory disease?Lancet, 2: 789, 1977.
37.
Dormandy, J.A. , Hoare, E., Khattab, A.H., et al.: Prognostic significance of rheological and biochemical findings in patients with intermittent claudication. Br. Med. J., 4: 581, 1973.
38.
Merrill, E.W. : Rheology of the blood. Physiol. Rev., 49: 863, 1969.
39.
Rosenblum, W.I.: Viscosity plus effect in whole blood at high shear rates. Nature, 221: 365, 1969.
40.
Weed, R.I., Bowdler, A.J.: Metabolic dependence of the critical hemolytic volume of human erythrocytes: Relationship to osmotic fragility and autohemolysis in hereditary spherocytosis and normal red cells. J. Clin. Invest., 45: 1137, 1966 .
