Norepinephrine and E139 interactions on epileptiform activity in the rat hippocampus in vitro.
OBJECTIVE
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.


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%).


CONCLUSIONS
E139 suppressed population responses and in vitro epileptiform activity by both adrenergic and non-adrenergic mechanisms.
Kombian
Samuel B
SB
Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait. kombian@hsc.edu.kw
Ananthalakshmi
Kethireddy V V
KV
Edafiogho
Ivan O
IO
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003510:Cyclohexanes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000927:Anticonvulsants; D003510:Cyclohexanes; C482385:E139 compound; D015016:Yohimbine; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine