去甲肾上腺素与E139对大鼠海马体癫痫样活动的体外相互作用。

Kombian Samuel B, Ananthalakshmi Kethireddy V V, Edafiogho Ivan O

Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait.

Med Princ Pract. 2008;17(5):365-72. doi: 10.1159/000141499. Epub 2008 Aug 6.

OBJECTIVES

We tested if E139, an anticonvulsant enaminone, interacts with norepinephrine (NE) to suppress population responses and chemically induced in vitro seizures in the rat hippocampus.

MATERIALS AND METHODS

Evoked field population spikes (PS) were recorded in the hippocampal CA1 area, and in vitro seizures were generated chemically using the zero Mg(2+) model.

RESULTS

Low concentrations of E139 (<or=10 microM) reversibly inhibited PS amplitude while high concentrations (>or=100 microM) enhanced them. For example, E139 (10 microM) depressed the PS amplitude by -23.9 +/- 2.3%, while 1 mM caused an enhancement. NE also depressed the PS by -34.5 +/- 6.0% and prevented E139 from subsequently depressing the PS amplitude. UK 14304, a selective alpha(2)-adrenoceptor agonist, also depressed the PS amplitude by -32.6 +/- 9.4% and occluded E139 suppression. NE suppression of PS was blocked by phentolamine and yohimbine which also blocked the effect of E139. Prazosin, a selective alpha(1)-adrenoceptor antagonist, did not block NE (-24.8 +/- 6.9%) or E139 (-29.7 +/- 6.1%) effects. Zero Mg(2+) buffer transformed a single PS to multiple spikes (MS; 3-8 spikes) and also induced spontaneous bursts (SB; 5-20/min). NE suppressed the number of MS from 5.6 +/- 0.3 to 3.8 +/- 0.2. At its peak effect, E139 was able to further suppress the number of MS to 3.0 +/- 0.3. Yohimbine did not change the number of MS but blocked the NE- and E139-induced suppression of MS. SB frequency was suppressed by NE (-60.8 +/- 11.7%) which occluded E139 effects. Finally, SB were reversibly abolished by yohimbine (-94.5 +/- 11.7%).

CONCLUSION

E139 suppressed population responses and in vitro epileptiform activity by both adrenergic and non-adrenergic mechanisms.

目的

我们测试了抗惊厥烯胺酮E139是否与去甲肾上腺素（NE）相互作用，以抑制大鼠海马体中的群体反应和化学诱导的体外癫痫发作。

材料与方法

在海马CA1区记录诱发场群体峰电位（PS），并使用零镁（2+）模型化学诱导体外癫痫发作。

结果

低浓度的E139（≤10微摩尔）可逆性抑制PS幅度，而高浓度（≥100微摩尔）则增强PS幅度。例如，E139（10微摩尔）使PS幅度降低-23.9±2.3%，而1毫摩尔则导致增强。NE也使PS降低-34.5±6.0%，并阻止E139随后降低PS幅度。UK 14304，一种选择性α（2）-肾上腺素能受体激动剂，也使PS幅度降低-32.6±9.4%，并阻断E139的抑制作用。酚妥拉明和育亨宾阻断了NE对PS的抑制作用，也阻断了E139的作用。哌唑嗪，一种选择性α（1）-肾上腺素能受体拮抗剂，未阻断NE（-24.8±6.9%）或E139（-29.7±6.1%）的作用。零镁（2+）缓冲液将单个PS转变为多个峰电位（MS；3-8个峰电位），并诱导自发爆发（SB；5-20次/分钟）。NE将MS的数量从5.6±0.3减少到3.8±0.2。在其峰值效应时，E139能够进一步将MS的数量减少到3.0±0.3。育亨宾没有改变MS的数量，但阻断了NE和E139诱导的MS抑制。SB频率被NE抑制（-60.8±11.7%），这阻断了E139的作用。最后，育亨宾可逆性消除了SB（-94.5±11.7%）。