DEVELOPMENT OF TOLERANCE TO THE ANTICONVULSANT EFFECT OF VALPROATE BUT NOT TO ETHOSUXIMIDE IN A RAT MODEL OF ABSENCE EPILEPSY

被引:16
作者
WAHLE, H [1 ]
FREY, HH [1 ]
机构
[1] FREE UNIV BERLIN,SCH VET MED,DEPT PHARMACOL & TOXICOL,KOSERSTR 20,W-1000 BERLIN 33,GERMANY
关键词
Absence model (in rats); Ethosuximide; Tolerance; Valproate;
D O I
10.1016/0014-2999(90)90238-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Ethosuximide and valproic acid were tested for 4 and 2 weeks, respectively, in rats showing the spontaneous spike-wave syndrome. Ethosuximide suppressed the syndrome at plasma concentrations of 75-100 μg/ml. High doses of valproate (170 mg/kg i.p., t.i.d.), resulting in plasma concentrations of about 500 μg/ml, were necessary to suppress the syndrome, but signs of tolerance to the drug developed from day 5. Tolerance was confined to the number of spike-wave complexes, whereas the duration of the discharges was shortened to 60% of the control value, without there being signs of tolerance. It is assumed that increases in cerebral GABA, induced by the high concentration of valproate, counteracted the anti-absence effect of the drug in this model. © 1990.
引用
收藏
页码:1 / 8
页数:8
相关论文
共 19 条
[1]  
EADIE MJ, 1989, PHARM BASIS PRACTICE, P219
[2]  
ELSAYED MA, 1978, ARCH INT PHARMACOD T, V234, P180
[3]  
Frey H.-H., 1985, HDB EXPT PHARM, V74, P265
[4]  
FREY HH, 1987, POL J PHARMACOL PHAR, V39, P495
[5]  
HARDING GFA, 1978, EPILEPSIA, V19, P555, DOI 10.1111/j.1528-1157.1978.tb05036.x
[6]   THE EPILEPTIC NATURE OF RODENT ELECTROCORTICAL POLYSPIKING IS STILL UNPROVEN [J].
KAPLAN, BJ .
EXPERIMENTAL NEUROLOGY, 1985, 88 (02) :425-436
[9]  
LOSCHER W, 1989, J PHARMACOL EXP THER, V250, P1067
[10]  
LOSCHER W, 1978, J PHARMACOL EXP THER, V204, P255