Anticonvulsant profile of flunarizine and relation to Na+ channel blocking effects

Basic and Clinical Pharmacology and Toxicology

Volumn 94, Issue 2, 2004, Pages 79-88

  Fischer, Wolfgang ^a   Kittner, Holger ^a   Regenthal, Ralf ^a   De Sarro, Giovambattista ^b  

^a UNIVERSITY OF LEIPZIG   (Germany)

^b UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICONVULSIVE AGENT; CARBAMAZEPINE; FLUNARIZINE; PENTETRAZOLE; PHENYTOIN; SODIUM CHANNEL; SODIUM CHANNEL BLOCKING AGENT; 1,4 DIHYDRO 2,6 DIMETHYL 5 NITRO 4 [2 (TRIFLUOROMETHYL)PHENYL] 3 PYRIDINECARBOXYLIC ACID METHYL ESTER; CALCIUM CHANNEL BLOCKING AGENT; CALCIUM CHANNEL STIMULATING AGENT; CONVULSANT AGENT;

AMYGDALOID NUCLEUS; ANIMAL MODEL; ANIMAL TISSUE; ANTICONVULSANT ACTIVITY; ARTICLE; BRAIN DEPTH STIMULATION; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; ELECTRIC SHOCK; EPILEPSY; HEART MUSCLE CELL; HIPPOCAMPUS; MOUSE; NONHUMAN; PATCH CLAMP; PRIORITY JOURNAL; SODIUM CURRENT; TONIC CLONIC SEIZURE; ANIMAL; BRAIN; CELL CULTURE; CHEMICALLY INDUCED DISORDER; DOSE RESPONSE; DRUG EFFECT; DRUG INTERACTION; MALE; METABOLISM; RAT; ROTAROD TEST; SEIZURE; WISTAR RAT;

ANIMALIA; MUS; RATTUS;

3-PYRIDINECARBOXYLIC ACID, 1,4-DIHYDRO-2,6-DIMETHYL-5-NITRO-4-(2-(TRIFLUOROMETHYL)PHENYL)-, METHYL ESTER; ANIMALS; ANTICONVULSANTS; BRAIN; CALCIUM CHANNEL AGONISTS; CALCIUM CHANNEL BLOCKERS; CELLS, CULTURED; CONVULSANTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INTERACTIONS; ELECTROSHOCK; FLUNARIZINE; MALE; MICE; PENTYLENETETRAZOLE; RATS; RATS, WISTAR; ROTAROD PERFORMANCE TEST; SEIZURES; SODIUM CHANNELS;

EID: 1642317928     PISSN: 17427835     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1742-7843.2004.pto940205.x     Document Type: Article

References (73)

1. 1 receptors. Eur. J. Pharmacol. 1991, 197, 221-223.
2. Ashton, D. & A. Wauquier: Behavioral analysis of the effects of 15 anticonvulsants in the amygdaloid kindled rat. Psychopharmacology 1979, 65, 7-13.
3. Bebin, M. & T. B. Bleck: New anticonvulsant drugs. Focus on flunarizine, fosphenytoin, midazolam and stiripentol. Drugs 1994, 48, 153-171.
4. Becker, A. & G. Grecksch: Flunarizine - its effect on pentylenetetrazol-kindled seizures and on related cognitive disturbances. Pharmacol. Biochem. Behav. 1995, 52, 765-769.
5. Belforte, J. E., C. Magarinos-Azcone, I. Armando, W. Buno & J. H. Pazo: Pharmacological involvement of the calcium channel blocker flunarizine in dopamine transmission at the striatum. Parkinsonism Rel. Disord. 2001, 8, 33-40.
6. Bingmann, D. & E. J. Speckmann: Specific suppression of pentyleneterazol-induced epileptiform discharges in CA3 neurons (hippocampal slice, guinea pig) by the organic calcium antagonists flunarizine and verapamil. Exp. Brain Res. 1989, 74, 239-248.
7. Binnie, C. D.: Potential antiepileptic drugs. Flunarizine and other calcium entry blockers. In: Antiepileptic drugs. Eds.: R. Levy, R. Mattson, B. Meldrum, J. K. Penry & F. E. Dreifuss. Raven Press, New York, USA, 1989, pp. 971-982.
8. Binnie, C. D. F. De Beukelaar, J. W. A. Meijer, H. Meinardi, J. Overweg, A. Wauquier & A. Van Wieringen: Open dose-ranging trial of flunarizine as add-on therapy in epilepsy. Epilepsia 1985, 26, 424-428.
9. + channels: local anesthetics, antiarrhythmics and anticonvulsants. Trends Pharmacol. Sci. 1987, 8, 57-65.
10. Chaisewikul, R., N. Baillie & A. G. Marson: Calcium antagonists as add-on therapy for drug-resistant epilepsy (Cochrane review). Cochrane Database Syst. Rev. 2001, 4, CD002750.
11. Czuczwar, S. J., M. Gasior, W. Janusz & Z. Kleinrok: Influence of flunarizine, nicardipine and nimodipine on the anticonvulsant activity of different antiepileptic drugs in mice. Neuropharmacology 1992, 31, 1179-1183.
12. Czyrak, A., E. Mogilnicka & J. Maj: Some central pharmacological effects of the calcium channel antagonist flunarizine. J. Neural Transm. 1991, 83, 179-188.
13. De Bock, G. H., J. Eelhart, H. W. J. Van Marwijk, T. P. Tromp & M. P. Springer: A postmarketing study of flunarizine in migraine and vertigo. Pharm. World Sci. 1997, 19, 269-274.
14. Desai, C. K., R. K. Dikshit, S. M. Mansuri & U. H. Shah: Comparative evaluation of anticonvulsant activity of calcium channel blockers in experimental animals. Ind. J. Exp. Biol. 1995, 33, 931-934.
15. De Sarro, G. B., C. Ascioti, E. Donato di Paola, M. J. Vidal & A. De Sarro: Effects of antiepileptic drugs, calcium channel blockers and other compounds on seizures induced by activation Of voltage-dependent L calcium channel in DBA/2 mice. Gen. Pharmacol. 1992a, 23, 1205-1216.
16. De Sarro, G. B., A. De Sarro, G. R. Trimarchi & G. Nisticò: Effects of some calcium antagonists upon the activity of common anti-epileptic compounds on sound-induced seizures in DBA/2 mice. Gen. Pharmacol. 1992b, 23, 75-82.
17. De Sarro, G. B., G. Nisticò & B. S. Meldrum: Anticonvulsant properties of flunarizine on reflex and generalized models of epilepsy. Neuropharmacology 1986, 25, 695-701.
18. De Sarro, G. B., E. Ongini, R. Bertorelli, U. Aguglia & A. De Sarro: Anticonvulsant activity of 5,7DCKA, NBQX and felbamate against some chemoconvulsants in DBA/2 mice. Pharmacol. Biochem. Behav. 1996, 55, 281-287.
19. Desmedt, L. K. C., C. J. E. Niemegeers & P. A. J. Janssen: Anticonvulsant properties of cinnarizine and flunarizine in rats and mice. Arzneimittelforsch./Drug Res. 1975, 25, 1408-1413.
20. Drago, E, C. Valerio, G. Clementi & U. Scapagnini: Effects of flunarizine on experimentally-induced convulsions in animals. Fund. Neurol. 1986, 1, 529-532.
21. Dunham, N. W. & T. S. Miya: A note on a simple apparatus for detecting neurological deficit in rats and mice. J. Amer. Pharm. Assoc. 1957, 46, 208-209.
22. Fischer, W.: Einfluß von Flunarizin auf die antikonvulsive Wirksamkeit von Phenobarbital beim maximalen Elektrokrampf der Maus. Pharmazie 1978, 42, 743-744.
23. Fischer, W.: Calcium and sodium channel inhibitors and modulation of the effectiveness of standard antiepileptic drugs. Naunyn-Schmiedebergs Arch. Pharmacol 1993, 348 (Suppl.), R151.
24. Fischer, W.: Pharmakologische Modulation noradrenerger und membranstabilisierender Mechanismen. Möglichkeiten zur Beeinflussung der Effektivität von Standardantiepileptika. Thesis (Habilitationsschrift). Martin-Luther-Universität, Halle-Wittenberg, 1995.
25. Fischer, W.: Anticonvulsant profile and mechanism of action of propranolol and its two enantiomers. Seizure 2002, 11, 285-302.
26. 2+-Kanalblocker und Referenzsubstanzen beim maximalen Elektrokrampf der Maus. Pharmazie 1987, 42, 420-421.
27. Fischer, W., R. Bodewei, P. F. VonVoigtlander & M. Müller: Anticonvulsant and related effects of U-54494A in various seizure tests. J. Pharmacol. Exp. Therap. 1993, 267, 163-170.
28. Fischer, W., H. Kittner, R. Regenthal, B. Malinowska & E. Schlicker: Anticonvulsant and sodium channel blocking activity of higher doses of clenbuterol. Naunyn-Schmiedebergs Arch. Pharmacol. 2001, 363, 182-192.
29. Fraser, A. D.: New drugs for the treatment of epilepsy. Clin. Biochem. 1996, 29, 97-110.
30. Fröscher, W., P. Bülau, W. Burr, V. Hoffmann, H. Kiefer, K. Kreiten, B. Nikelowski, H. Penin & M. L. Rao: Development of tolerance to the anticonvulsant effects of flunarizine and its side effects? Clinical, psychometric, EEG and biochemical approaches. In: Tolerance to beneficial and adverse effects of antiepileptic drugs. Eds.: H. H. Frey, W. Fröscher, W. P. Koella & H. Meinardi. Raven Press, New York, USA, 1986, pp. 137-147.
31. Gasior, M., R. Kaminski, T. Brudniak, Z. Kleinrok & S. J. Czuczwar: Influence of nicardipine, nimodipine and flunarizine on the anticonvulsant efficacy of antiepileptics against pentylenetetrazol in mice. J. Neural Transm. 1996, 103, 819-831.
32. Hamill, O. P., A. Marty, E. Neher, B. Sakmann & F. J. Sigworth: Improved patch-clamp techniques for high-resolution current recording from cell and cell-free membrane patches. Pflügers Arch. Eur. J. Physiol. 1981, 391, 85-110.
33. Handforth, A., T. Mai & D. M. Treiman: Rising dose study of safety and tolerance of flunarizine. Eur. J. Pharmacol. 1995, 49, 91-94.
34. Holmes, B., R. N. Brogden, R. C. Heel, T. M. Speight & G. S. Avery: Flunarizine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use. Drugs 1984, 27, 6-44.
35. Hoppu, K., A. R. Nergardh, A. S. Eriksson, O. Beck, E. Forssblad & L. O. Boreus: Flunarizine of limited value in children with intractable epilepsy. Pediat. Neurol. 1995, 13, 143-147.
36. Joseph, S., J. David & T. Joseph: Additive anticonvulsant effect of flunarizine and sodium valproate on electroshock and chemoshock induced seizures in mice. Ind. J. Physiol. Pharmacol. 1998, 42, 383-388.
37. +-channel blockers in isolated Purkinje neurons of rat cerebellum. Neuroscience 1993, 54, 575-585.
38. Lapin, I. P. & I. V. Ryzov: Effect of catecholaminergic drugs on quinolinate- and kynurenine-induced seizures in mice. J. Neural Transm. 1990, 82, 55-65.
39. Litchfield, Jr., J. T. & F. Wilcoxon: A simplified method of evaluating dose-effect experiments. J. Pharmacol. Exp. Therap. 1949, 96, 99-113.
40. Löscher, W. & D. Schmidt: Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations. Epilepsy Res. 1988, 2, 145-181.
41. Mack, C. M. & M. E. Gilbert: An examination of the anticonvulsant properties of voltage-sensitive calcium channel inhibitors in amygdala kindled seizures. Psychopharmacology 1992, 106, 365-369.
42. Mahmood, I., V. K. Tammara, & R. K. Baweja: Does percent reduction in seizure frequency correlate with plasma concentration of anticonvulsant drugs? Experience with four anticonvulsant drugs. Clin. Pharmacol. Therap. 1998, 64, 547-552.
43. Michiels, M., R. Hendriks, F. Knaeps, R. Woestenborghs & J. Heykants: Absorption and tissue distribution of flunarizine in rats, pigs and dogs. Arzneimittelforsch./Drug Res. 1983, 33(II), 1135-1142.
44. Moron, M. A., C. W. Stevens, & T. L. Yaksh: Diltiazem enhances and flunarizine inhibits nimodipine's antiseizure effects. Eur. J. Pharmacol. 1989, 163, 299-307.
45. Moron, M. A., C. W. Stevens, & T. L. Yaksh: The antiseizure activity of dihydropyridine calcium channel antagonists in the conscious rat. J. Pharm. Exp. Therap. 1990, 252, 1150-1155.
46. Nakane, Y., M. Seino, K. Yagi, S. Kaji & T. Yamauchi: Effects of flunarizine therapy on intractable epilepsy. Arzneimittelforsch./Drug Res. 1989, 39(II), 793-798.
47. Overweg, J. & C. D. Binnie: Flunarizine. In: Comprehensive epileptology. Eds.: M. Dam & L. Gram. Raven Press, New York, USA, 1990, pp. 655-664.
48. Palmer, G. C., M. L. Stagnitto, R. K. Ray, M. A. Knowles, R. Harvey & G. E. Garske: Anticonvulsant properties of calcium channel blockers in mice: N-methyl-D-L-aspartate- and Bay K 8644-induced convulsions are potently blocked by the dihydropyridines. Epilepsia 1993, 34, 372-380.
49. + channels involved in neuronal cell death. Protection by flunarizine. Life Sci. 1991, 48, 1881-1893.
50. Pledger, G. W., J. C. Sackellares, D. M. Treiman, J. M. Pellock, F. S. Wright, M. Mikati, J. T. Sahlroot, J. Y. Tsay, M. E. Drake, L. Olson, C. A. Handforth, W. R. Garnett, S. Schachter, H. J. Kupferberg, M. R. Ashworth, C. McCormick, D. Leiderman, I. M. Kapetanovic, S. Driscoll, K. O'Hara, C. D. Torchin, J. Gentile, A. Kay & J. J. Cereghino: Flunarizine for treatment of partial seizures: results of a concentration-controlled trial. Neurology 1994, 44, 1830-1836.
51. Pohl, M. & P. Mareš: Influence of flunarizine on hippocampal epileptic afterdischarges in the rat. Physiol. Res. 1994, 43, 57-60.
52. Popoli, P., A. Pèzzola & A. Scotti de Carolis: Possible involvement of the adenosinergic system in flunarizine anticonvulsant activity in rats. Arch. Int. Pharmacodyn. Ther. 1990, 306, 45-56.
53. Racine, R. J.: Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroenceph. Clin. Neurophysiol. 1972, 32, 281-294.
54. Rho, J. M. & R. Sankar: The pharmacological basis of antiepileptic drug action. Epilepsia 1999, 40, 1471-1483.
55. Rogawski, M. A. & R. J. Porter: Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacol. Rev. 1990, 42, 223-286.
56. Sabers, A. & L. Gram: Drug treatment of epilepsy in the 1990s. Achievements and new developments. Drugs 1996, 52, 483-493.
57. Schmidt, J.: Comparative studies on the anticonvulsant effectiveness of nootropic drugs in kindled rats. Biomed. Biochim. Acta 1990, 49, 413-419.
58. Schwartzkroin, P. A. & A. R. Wyler: Mechanisms underlying epileptiform burst discharge. Ann. Neurol. 1980, 7, 95-107.
59. Serra, M., L. Dazzi, M. Caddeo, C. Floris & G. Biggio: Reversal by flunarizine of the decrease in hippocampal acetylcholine release in pentylenetetrazole-kindled rats. Biochem. Pharmacol. 1999, 58, 145-149.
60. Speckmann, E.-J., H. Straub & R. Köhling: Contribution of calcium ions to the generation of epileptic activity and antiepileptic calcium antagonism. Neuropsychobiology 1993, 27, 122-126.
61. 2+ in neocortical tissue of epileptic and primary non-epileptic patients. Brain Res. 1996, 733, 307-311.
62. Subramanyam, K., J. David & T. Joseph: Interaction of flunarizine with sodium valproate or ethosuximide in gammahydroxybutyrate induced absence seizures in rats. Ind. J. Exp. Biol. 2001, 39, 998-1001.
63. Todd, P. A. & P. Benfield: Flunarizine. A reappraisal of its pharmacological properties and therapeutic use in neurological disorders. Drugs 1989, 38, 481-499.
64. Trommer, B. L. & J. F. Pasternak: Flunarizine does not delay the development of generalized seizures by amygdala kindling. Epilepsy Res. 1989, 4, 230-233.
65. Tytgat, J., P. J. Pauwels, J. Vereecke & E. Carmeliet: Flunarizine inhibits a high-threshold inactivating calcium channel (N-type) in isolated hippocampal neurons. Brain Res. 1991, 549, 112-117.
66. Van Zwieten, P. A.: Differentiation of calcium entry blockers into calcium channel blockers and calcium overload blockers. Eur. Neurol. 1986, 25 (Suppl.1), 57-67.
67. Vezzani, A., H. Q. Wu, M. A. Stasi, P. Angelico & R. Samanin: Effect of various calcium channel blockers on three different models of limbic seizures in rats. Neuropharmacology 1988, 27, 451-458.
68. Waki, H., K. Kon, Y. Tanaka & S. Ando: Age-related changes in the uptake of calcium channel blockers by brain capillary endothelial cells and synaptosomal fractions. Neurosci. Lett. 1990, 116, 367-371.
69. Wallukat, G. & A. Wellenbergen Differential α- and β-adrenergic responsiveness of beating rat heart myocytes after stationary and non-stationary cultivation. Acta Biol. Med. Germ. 1980, 39, K7-K13.
70. Wang, R., E. Karpinski, L. Wu & P. K. T. Pang: Flunarizine selectively blocks transient calcium channel currents in N1E-115 cells. J. Pharmacol. Exp. Therap. 1990, 254, 1006-1011.
71. Wauquier, A., D. Ashton, G. Clincke, J. Fransen, J.-M. Gillardin & P. A. J. Janssen: Anticonvulsant profile of flunarizine. Drug Dev. Res. 1986, 7, 49-60.
72. Weizman, R., V. Getslev, I. A. Pankova, S. Schrieber & C. G. Pick: Pharmacological interaction of the calcium channel blockers verapamil and flunarizine with the opioid system. Brain Res. 1999, 818, 187-195.
73. Willow, M.: Pharmacology of diphenylhydantoin and carbamazepine action on voltage-sensitive sodium channels. Trends Neurosci. 1986, 9, 147-149.