Kinetics of drug action in disease states. XXXIII: Disparate effects of pentylenetetrazol in rats as a function of renal disease model and pharmacologic endpoint.
Kinetics of drug action in disease states. XXXIII: Disparate effects of pentylenetetrazol in rats as a function of renal disease model and pharmacologic endpoint.
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疾病状态下药物作用的动力学。
DOI：
10.1002/jps.2600780214
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发表时间：
1989
影响因子：
3.8
通讯作者：
Levy,G
中科院分区：
文献类型：
--
作者：
Ramzan,I;Levy,G
这项研究的目的是确定中枢神经系统刺激剂戊四唑(PTZ)在肾功能障碍时的药效学是否发生改变。双侧输尿管结扎(假手术对照组)或硝酸铀酰注射(生理盐水对照组)的雌性大鼠静脉注射PTZ，直到发作轻微(肌阵挛)或最大(强直后肢伸展)发作。在微小癫痫发作开始时，化学或手术引起的肾功能障碍都不会引起脑脊液、血清或脑内PTZ浓度的变化。当PTZ用于最大癫痫发作时，化学性肾功能障碍的大鼠需要较高的浓度，而输尿管结扎大鼠在较低浓度的PTZ下惊厥。因此，实验性肾功能障碍对PTZ惊厥作用的影响取决于疾病模型和用于药效学测量的终点。显然，肾功能障碍不影响PTZ诱导的癫痫阈值，但抑制癫痫的扩散。输尿管结扎大鼠的敏感性增加可能是因为它们显著地保留了水，因为众所周知水负荷增加了癫痫的易感性。
The purpose of this investigation was to determine if the pharmacodynamics of the central nervous system stimulant pentylenetetrazol (PTZ) are altered in renal dysfunction. Female rats subjected to bilateral ureteral ligation (with sham-operated controls) or injected with uranyl nitrate (with saline injected controls) were infused intravenously with PTZ until the onset of either a minimal (myoclonic jerk) or maximal (tonic hindlimb extension) seizure. Neither chemically nor surgically induced renal dysfunction caused a change in the concentrations of PTZ in CSF, serum, or brain at onset of minimal seizures. When PTZ was infused to onset of maximal seizures, the rats with chemically induced renal dysfunction required higher concentrations, whereas the ureterligated rats convulsed at lower concentrations of PTZ than did the corresponding control animals. Thus, the effects of experimental renal dysfunction on the convulsant action of PTZ are dependent on both the disease model and the endpoint used for the pharmacodynamic measurement. Apparently, renal dysfunction did not affect the PTZ-induced seizure threshold, but inhibited the spread of seizures. The increased sensitivity of ureterligated rats may be due to their pronounced retention of water, since water loading is known to increase seizure susceptibility.
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DOI：
--
发表时间：
1987
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Ramzan,IM;Levy,G
通讯作者：
Levy,G
改变血浆渗透压对大鼠脑部氨基酸浓度和局灶性癫痫易感性的影响
影响因子：
4.7
作者：
C. Baxter;C. Wasterlain;Kristine L. Hallden;Sharon F. Pruess
通讯作者：
Sharon F. Pruess
影响因子：
5
作者：
RAMANJANEYULU, R;TICKU, MK
通讯作者：
TICKU, MK
DOI：
--
发表时间：
1985
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Ramzan,IM;Levy,G
通讯作者：
Levy,G
DOI：
--
发表时间：
1984
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Danhof,M;Hisaoka,M;Levy,G
通讯作者：
Levy,G