PHARMACODYNAMIC INTERACTION BETWEEN NIFEDIPINE AND SODIUM VALPROATE AGAINST KAINIC ACID-INDUCED CONVULSOINS IN MICE دراسة التفاعالت الديناميکية الدوائية بين عقارى النيفيديبين وفالبروات الصوديوم ضد النوبات الصرعية المحدثة بمادة حامض الکاينيک فى الفئران | ||
| Assiut University Bulletin for Environmental Researches | ||
| Article 3, Volume 2.1, Issue 1, March 1999, Pages 31-43 PDF (192.93 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/auber.1999.141893 | ||
| Abstract | ||
| ABSTRACT : In the present study, the possible pharmacodynamic interaction between nifedipine (30 mg/kg,i.p) and sodium valproate (300 mg/kg,i.p) against kainic acid (70 mg/gk, i.p) was evaluated in mice. The seizures onset of kainic acid (KA), the percent of mice surviving KA-induced seizures and the mean survival time (MST) of mice were determined 30 minutes after single and combined administration of nifedipine and sodium valporate (VAL). The above mentioned three parameters of KA-induced seizures were determined in a control group of mice receiving saline solution. In a second set of experiments, the serum and brain Na+, Ca2+ and K+ ion contents were determined after single i.p. administration of KA, nifedipine and VAL. Two lesser than the MST of mice receiving KA, mice were given nifedipine plus KA, VAL plus KA and nifedipine plus VAL and KA. Serum and brain tissue samples were taken from all groups of mice and were analysed for their content of Na+, Ca2+ and K+ ion Results of this study revealed that the i.p injection of KA into mice led to the appearance of convulsions (seizure onset) after 6.06 minutes and a MST of mice of 7.82. minutes. This convulsive effect was associated with significant increase in brain Na+ and Ca+2 levels as well as significant lowering of brain K+ concentration. Our results also indicated that the i.p. injection of nifedipine into mice produced significant increase in the seizure onset of KA action and the MST of mice as well as, the percent protection of mice to a value of 25%. The anticonvulsant action of VAL was accompanied by a significant increase in the serum Na+ and Ca2+ contents and an elevated brain K+ level. In addition, our results indicated that the single i.p injection of VAL elicited significant increases in the onset of KA-induced seizures, the MST of mice as well the KA-induced mortality by a factor of 50%. This effect was correlated with an increase in the serum Na+, lowered brain Na+ and an increased brain K+. The combined administration of nifedipine and VAL was found to protect all animals from KA-induced death. This 100% protection was associated with 4-fold increase in the onset of KA-induced seizures. Measurement of the serum and brain electrolytes in mice receiving the combination of nifedipine and VAL demonstrated that this combination caused significant diminution of brain Na+ and Ca2+ ions and a rise in brain K+ ions. It may be the ability of nifedipine to reduce brain Na+ and Ca2+ concentration which is the factor responsible for the additive anticonvulsant effect recorded after the combined administration of nifedipine and sodium valproate فى ھذا البحث تم دراسة التفاعالت الديناميکية الدوائية المحتملة بين عقارى النيفيديبين وفالبروات الصوديوم ضد النوبات الصرعية المحدثة بواسطة مادة حامض الکاينيک . -وتم قياس الزمن الالزم لظھور النوبات التشنجية ونسبة الموت فى حيوانات التجارب باإلضافة إلى متوسط األزمنة التى تبقى فيه الفئران حيه بعد حقن مادة حامض الکاينيک لوحدھا وبعد مرور ٣٠ دقيقة من حقن کل من النيفيدبين وفالبروات الصوديوم کل على حده أو فى تعاطى مشترک. - وکذلک تم قياس مستوى أيونات الصوديوم والکالسيوم والبوتاسيوم فى مصل ومخ الفئران بعد الحقن البريتونى لکل من حامض الکاينيک والنيفيديبن وفالبروات الصوديوم قبل انتھاء زمن بقاء الحيوانات حيه وعقب حقنھا بحامض الکاينيک بدقيقتين . - أظھرت النتائج أن حقن حامض الکاينيک فى الفئران يؤدى إلى ظھور نوبات صرعية بعد زمن ٦٫٠٦ دقيقة من حقن المادة وأن متوسط زمن بقاء الحيوانات حيه قد وصل إلى ٧٫٨٢ دقيقة. ً أن ھذه النوبات الصرعية تکون مصحوبة بزيادة ملحوظة فى مستوى وأظھرت النتائج أيضا الصوديوم والکالسيوم ونقص فى مستوى البوتاسيوم فى مخ الفئران. وکذلک يؤدى إلى زيادة نسبية فى الزمن الالزم لبدء حدوث النوبات الصرعية وزمن بقاء الحيوانات حيه باالضافة إلى زيادة فى نسبة حماية الحيوانات من الموت بعد حقن مادة حامض الکاينيک (٢٥%). ً فإن ھذه الدراسة أثبتت أن حقن مادة فالبروات الصوديوم بمفردھا قد أدى إلى زيادة نسبية فى - أيضا الزمن الالزم لظھور النوبات التشنجية للفئران وزمن بقاء الحيوانات حيه عقب حامض الکاينيک ھذا باالضافة إلى زيادة فى نسبة حماية الحيوانات من الموت بنسبة ٥٠%. وقد کانت ھذه التأثيرات المضادة للتشنج مصحوبة بزيادة فى مستوى الصوديوم فى مصل الفئران ونقص فى مستوى الصوديوم والکالسيوم وزيادة فى مستوى البوتاسيوم فى المخ. وعند الحقن المشترک لعقارى النفيديبين وفالبروات الصوديوم أدى ذلک إلى حماية کل حيوانات التجارب من الموت المحدث بحامض الکاينيک مع زيادة فى الزمن الالزم لبدء حدوث النوبات مصحوبا بنقص فى مستوى الصوديوم والکالسيوم وزيادة فى مستوى ً التشنجية وکان ھذا التأثير البوتاسيوم فى مخ الفئران. | ||
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