Belcheva, A.

Borisova, P.

Chaldakov, G.

Yordanov, V.

Zhelyazkov, D.

English

Varna Medical University Press: Journals

I . E X P E R I M E N T A L P R O B L E M S S T U D Y OF COLCHICINE E F F E C T S ON E L E C T R O C O N V U L S I V E E P I L E P T I C E Q U I V A L E N T IN RATS V. Yordanov, P. Borisova, A. Belcheva, G, Chaldakov, D. Zhelyazkov Key-words: colchicine — epileptic equivalent - phenobarbital -anticonvulsive action — rats I t is generally accepted that each anticonvulsive drug has to be tested in dif-ferent conditions correlating with basic forms of the epileptic disease. I t is, there-fore, necessary for the following reasons: 1. The therapeutic spectrum of the new drug has to be clarified; 2. Some mechanisms of anticonvulsive action of the drug have to be reveal-ed; 3. Some essential mechanisms of epileptic equivalents have to be clarified. The present work continues our previous investigations where it was proved that intraperitoneally injected colchicine at dosage of 2,5 mg/kg b. w. reduced convulsive signs caused by corazol at dosage of 70 mg/kg b. w. (1). ; The idea which conceived these studies is based on the fact that colchicine — an agenl destructing specifically cytoplasmic imicrotubules (2, 3, 4) — is widely used concerning the relation of these cell structures towards different physiolo-gical phenomena fcand pathological abnormalities. This communication presents some data about colchicine effect on convulsive signs induced by electric current in rats. . Material and methods White male rats with b. w. 150—200 g were used in our study. The animals were divided into two experimental groups: 1 s t — only once treated with colchi-cine, and I I n d — many times treated with colchicine ones. In the 1 s t group the animals were intraperitoneally injected with 0,5, 1,25 and 2,5 mg/kg b. w. col-chicine. There was also a parallel experimental group with animals treated with 20 mg/kg b. w. phenobarbital. The animals of the second group were divided into following subgroups: 1 s t — controls (adequate intraperitoneal amounts of physiological saline), and then: 2 n d —wi th colchicine (0,5 mg/kg b. w. daily for 7 days, 3 r d — with phenobarbital (20 mg/kg b. w. daily for 7 days, and 4 t h — with combination of colchicine and phenobarbital at the same dosage and appli-cation as mentioned in group 2 n d and 3 r d . Drugs: Colchicine (Fluka A G , Buchs SG) diluted in physiological saline. 2. Phenobarbital natrium (Pharmachim, Sofia) diluted in destillated water. Electroconvulsions were induced with sinusoid current produced by current 10 V. Yordanov, P. Borisova. generator elaborated at the Dept. of Pharmacology and Dept. of Medical Physics of the Higher Institute of Medicine — Varna*. The electric current had following parameters: sinusoidal, frequency 50 Hz, Intensity between 10 and 40 mA, duration of irritation — 0,5 sec (5). Oral-occi-pital electrodes were used to let the current through the calvaria of the animals. Any animals were treated by gradually increasing current power (starting from 10 mA and causing a tonic electroconvulsion). The tonic convulsion was used as a criterion for estimation of the threshold of electric stimulation generalization (TESG) which was quantitatively measured in mA. T E S G was determined before and after colchicine, phenobarbital or physiological saline treatment. After each stroke the minimal restitution time was 15 min but after tonic convulsion induc­tion — 30 min. The results were statistically processed after Student-Fisher's method. Results and discussion The results are presented on table 1 and 2. I t can be seen that single colchi­cine treatment with three different doses 30, 120 and 240 min after injection does T a b l e 1 Threshhold of generalization of electrical stimulation after single treatment with col­chicine and phenobarbital as expressed in mA (n—10) Pretreat-ment time Colchicine 0,5 mg/kg Colchicine 1,25 mg/kg Colchicine 2,5 mg/kg Phenobarbital 20 mg/kg before treatment after treatment before treatment after treatment before treatment after treatment before treatm. after treatm-30 min 120 min 240 min 18,66 ±2,25 13, 9 ± 1 , 9 20,13±2,18 21,77±2,41 19, 9_3.41 23,41 ±4,14 23,30 ±2,03 20, 9 ± 2 , 6 17,55 ±2,96 23,45±4,Ю 21, 8±5 ,35 17,17_5.19 25,95 ±3,45.22, 5 ±4,06 16,71 ±2,07 16,79±4,15 10,84 ±1,67J 13,29 ±3,20 14,5 ±2 ,4 27,04 ±4 ,35 T a b l e 2 Threshold of generalization of electrical stimulation after repeated treatment with colchicine, colchicine and phenobarbital, and phenobarbital as expressed in mA Groups Before treatment After taeatment Physiological 18,75-3.06 18,82_=4,30 saline n=10 Colchicine 13,36-2,85 0,5 mg/kg n—14 Phenobarbital 16,78=-2,95 16,02=-3,80 0,20 mg/kg n - 1 4 Colchicine and 20,66-3,27 17,00=-4,03 phenobarbital n—12 * The elaboratotion is realized by R. Tsonchev, V . Yordanov and D. Zhelyazkov as &now-how and first applied in H I M —Varna. Study of colchine effects on. 11 not cause any statistical changes of T E S G of the experimental animals. However, after 20 mg/kg b. w. phenobarbital treatment there is a statistically significant nearly twofold T E S G increase. Repeated colchicine or combined treatment causes a tendency towards T E S G decrease. These results allow us to accept that con­cerning the electroconvulsive epileptic equivalent single colchicine treatment does not possess any anticonvulsive effect at different time intervals up to 4 hours. The data concerning repeated phenobarbital treatment where this "classi" anti-epileptic drug does not show any anticonvulsive effect in contrast to single treat­ment require a careful discussion. In this respect it has to be considered that the time of repeated phenobarbital application (7 days) is enough for it to induce hepatic drug metabolizing enzymes and to suppress its anticonvulsive action by accelerating its own metabolism. A l l the more that experiments to establish T E S G were performed 24 hours after last phenobarbital application. The lack of an anticonvulsive effect after single colchicine administration on electroconvulsive epileptic equivalent of the grand mal as used in the present work in contrast to the clearly expressed anticonvulsive effect in case of corazol epileptic equivalent of the petit mal (1) raises the interesting question about the differentiated relation of colchicine as potentially antiepileptic drug and/or "mo­dulator" of antiepileptic effects of some known anticonvulsive medicaments. I t is known that other antiepileptic drugs possess such a differentiated relation, too. Our study raises another interesting medico-theoretical problem: How far, if even it is so, the status of cytoskeleton, especially mainly of cytoplasmic microtubules and membrane bound tubulin of the nerve cell plays a role in the pre-determination of the clinical form of epilepsy? R E F E R E N C E S 1. Y o r d a n o v , V. N., А. В е 1 с h е v a, D. K. Z h е 1 у a z к о v, N. D e -l e v a , G. N. С h a 1 d а к о v. Plenum Press (in press). 2. W i l s o n , L . , M. F r i e d -k i n . Biochemistry, 6, 1967, 3126—З1З5. 3. В о r i s у, G . G . , E . W. T a y l o r . J. Cell Biol, 34, 1967, 525—534. 4. В о r i s у, G. G . , Е. W. T a y l o r . J . Cell Biol., 34, 1967, 535—547. 5. G r i s k, A. Praktikum der Pharmakologie und Toxikologie. Jena, Fischer Verlag, 1969, 70—71. ИССЛЕДОВАНИЕ ЭФФЕКТОВ КОЛХИЦИНА НА ЭЛЕКТРОСУДОРОЖНЫЙ ЭПИЛЕПТИЧЕСКИЙ ЭКВИВАЛЕНТ У КРЫС В. Йорданов, П. Борисова, А. Белчева, Г. Чалдыков, Д. Желязков Р Е З Ю М Е При более ранних наших исследованиях установлен антагонистический эффект колхи­цина на индуцированные коразолом судороги. Целью настоящей работы является изучение эффектов этого антимикротубулярного агента на электросудороги эпилептического эквива­лента у крыс. Животные подвергались однократному воздействию тремя различными дозами колхи­цина (0,5, 1,25, 2,5 мг/кг веса животных при интраперитонеальном введении) и многократ­ному воздействию в течение 7 дней дозами 0,5 мг/кг веса животных, введенными также ив> траперитонеально. Порог генерализации электрической стимуляции (ПГЭС) определялся до воздействия колхицином, а также в интервалах 3J ли , ioJ мин. и 240 мин. после его 12 V. Yordanov, P. Borisova. однократного введения. ПГЭС определялся и на восьмой день при многократном введении колхицина. Полученные результаты показывают, что после многократного введения колхицина на­блюдаются тенденции к понижению ПГЭС, в то время как после однократного его введения изменений ПГЭС не устанавливается. Обсуждается дифференцированное отношение колхицина к коразоловому и электро­судорожному эпилептическим эквивалентам пти мал и гранд мал, а также и роль цитоплаз-менных микротубул и мембранно-связанного тубулина нервной клетки в определении клини­ческих форм эпилепсии. 

STUDY OF COLCHICINE EFFECTS ON ELECTROCONVULSIVE EPILEPTIC EQUIVALENT IN RATS

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STUDY OF COLCHICINE EFFECTS ON ELECTROCONVULSIVE EPILEPTIC EQUIVALENT IN RATS

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