Flunarizinin omurilik reflekslerine etkisi
Amaç: Spinal kedilerde kalsiyum kanal blokeri flunarizinin monosinaptik reflekslere etkisini araştırmak amaçlandı. Yöntem: Flunarizin 10, 50, 100 uM lokal ve 5, 10, 20 mg/kg intraperitoneal olarak verildi. 1.5-3 kg ağırlığında yetişkin 10 kedi ketamin (50 mg/kg, İM) ile anestezi edildi ve suni ventilasyon uygulandı. Hayvanlar servikal (C1) seviyeden spinalize edildi. Lumbosakral bölgede laminektomi yapıldı. L5 segmentin dorsal ve ventral kökleri izole edildi. Havuz oluşturuldu, dokular likit vazelinle örtüldü ve 38.5+0.5°C'de muhafaza edildi. Karotis artere polietilen kanül yerleştirilerek kan basıncı gözlendi ve 100 mmHg'nın üzerinde olması sağlandı. Stimülasyon için L5 segmentin dorsal köküne gümüş-gümüş klorür tel elektrod yerleştirildi. Refleks potansiyeller ipsilateral L5 ventral kökten kaydedildi, bu kayıtta da gümüş-gümüş klorür tel elektrod kullanıldı. Bulgular: Flunarizinin sistemik ve lokal dozları refleks cevap amplitüdünü anlamlı şekilde azalttı. Bununla birlikte, ilaç uygulamasından sonra monosinaptik reflekslerin latensi uzadı. Sonuç: Omurilikteki voltaja bağımlı kalsiyum kanalları refleks cevabın düzenlenmesinde önemli bir role sahip olabilir.
The effects of flunarizine on spinal reflexes in the cats
Objective: Effects of calcium channel blocker flunarizine on spinal monosynaptic reflexes were aimed to investigate in spinal cats. Methods: Flunarizine was administered locally into the spinal cord (10, 50, 100 u.M) and intraperitoneally (5, 10, 20 mg/kg). Adult cats (n=10) weighing 1.5-3 kg were anesthetized with ketamine (50 mg/kg, IM) and artificially ventilated. Animals were spinalized at C1 level. A laminectomy was performed in the lumbosacral region. The ventral and dorsal roots of segment L5 were isolated and a pouch of skin was formed at the site of the dissection to allow the exposed tissues to be covered with liquid paraffin. The temperature was kept at 38.5±0.5°C with a heating pad. A polyethylene cannula was introduced into the left carotid artery to monitor blood pressure which was kept above 100 mmHg. The dorsal root of segment L5 was placed on a silver- silver chloride wire electrode for stimulation through an isolation unit. Reflex potentials were recorded from ipsilateral L5 ventral root, mounted on a silver- silver chloride wire electrode. Results: The systemic and local doses of cinnarizine derivative flunarizine significantly decreased the amplitude of reflex response. Moreover, the latency of the monosynaptic reflexes increased after administration of the drug. Conclusion: Voltage-dependent calcium channels in the spinal cord may play an important role in regulation the reflex response.
___
- Weiner DA. Calcium channel blockers. Med Clin Nort Amer 1988;72:83-115.
- Mikkelson EO. Calcium channel blockers (calcium antagonists): Background, effects and use. Ugeskr Laeger 1995;157:3750-4.
- Katz AM. Basic cellular mechanisms of action the calcium channel blockers. Am J Cardiol 1985;55:2B-9B.
- Ferlinz J. Nifedipine in myocardial ischemia, systemic hypertension and other cardiovasculer disorders. Ann Intern Med 1986;105:714-29.
- Tytgat J, Vereecke J, Carmeliet E. Differential effects of verapamil and flunarizine an cardiac L-type and T- type Ca channels. Arch Pharmacol 1988;337:690-2.
- McLean MJ. In vitro electrophysiological evidence predicting anticonvulsant efficacy of memantine and flunarizine. Pol J Pharmacol Pharm 1987;39:513-25.
- Kawasaki K, Takesue H, Matsushita A. Modulation of spinal reflex activities in acute spinal rats with alfa adrenergic agonists and antagonists. Jap J Pharmac 1978:28;165-8.
- Nagano N, Ono H, Fukuda H. Functional significance of subtypes of 5-HT receptors in the rat spinal reflex patway. Gen Pharmac 1988;19:789-93.
- Genç O, Taşçı N, Marangoz C. The effects of calcium channel blocker nifedipine on spinal reflexes in the cats. First European Congress of Pharmacology, Pharmacological Research, Abstract Book, 1995. p.226.
- Fujii S, Kameyama K, Hosono M, Hayashi Y, Kitamura K. Effect of cilnidipine, a novel dihydro pyridine Ca++-channel antagonist, on N-type Ca++ channel in rat dorsal root ganglion neurons. J Pharmacol Exp The 1997;280:1187-91.
- Binnie CD. Flunarizine in epilepsy. Ann N Y Acad Sci 1988;522:710-1.
- Aicardi G, Schwartzkroin PA. Supression of epileptiform burst discharges in CA3 neurons of rat hippocampal slices by the organic calcium channel blockers verapamil. Exp Brain Res 1990;81:288-96.
- Straub H, Baker RE, Bingman D, Speckmann EJ. Spontaneously appearing burst discharges in hippocampal and neocortical neurons (in vitro) supression by the calcium antagonist verapamil and flunarizine. Pflügers Arch 1991;Suppl 1:418.
- Straub H, Danz C, Speckmann EJ. Depressive effects of organic calcium antagonists on bicuculline induced epileptic activity in hippocampal and neocortical neurons. In: Speckmann EJ, Gutnick MJ, editors. Epilepsy and inhibition. München: Wien; 1992. p.255-70.
- Gan’shina TS, Mirzoian NR. The effect of calcium channel blockers on activity in the sympathetic nerves, on the vasomotor reflex and cerebral circulation. Exp Clin Pharmacol 1996;59:12-7.
- De Sarro GB, Meldrum BS, Nistico G. Anticonvulsant effects of some calcium entry blockers in DBA/2 mice. Br J Pharmac 1988;93:247-56.
- Popoli P, Pezzola A, Scotti de Carolis A. Effects of calcium antagonist nimodipine on pentylenetetrazol induced seizures in rats and rabbits. Arch Int Pharmacodyn Ther 1988;292:58-67.
- Moraidis I, Bingmann D, Lehmenkühler A, Speckmann EJ. Caffeine induced epileptic discharges in CA3 neurons of hippocampal slices of the guinea pig. Neurosci Lett 1991;129:51-4.
- E, Lux HD. A low voltage activated, fully inactivating calcium channel in vertabrate sensory neurons. Nature 1984;310:501-2.
- Carbone E, Lux HD. Kinetics and selectivity of a low voltage activated calcium current in chick and rat sensory neurons. J Physiol 1987a;386:547-70.
- Carbone E, Lux HD. Single low voltage activated calcium channels in chick and rat sensory neurons. J Physiol 1987b;386:571-601.
- Nowycky MC, Fox AP, Tsien RW. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature 1985;31b:339-43.
- Leysen JM, Gommeren W. In vitro binding profile of drugs used in migraine. In: Amery WK, Van Nueten JM, editors. The pharmacological basis of migraine therapy. London: A Wauquier Pitman; 1984. p. 255-67.
- Gould RJ, Murphy KMM, Snyder SH. Tissue heterogeneity of calcium channel antagonist binding sites labeled by (3H) nitrendipine. Mol Pharmacol 1984;25:235-41.