Synergistic protection of allopregnanolone and phenobarbital against maximal electroshock seizures in mice.
OBJECTIVE
To examine the interactions of allopregnanolone and phenobarbital for the protection against seizures.


METHODS
The protective activity of allopregnanolone and/or phenobarbital against seizures was studied in the C57 mice, using the maximal electroshock seizure (MES) test. The modulations by allopregnanolone and/or phenobarbital at the GABA(A) receptor were also characterized using the [3H]flunitrazepam binding in the membrane preparation of mouse cerebral cortex.


RESULTS
Pretreatment with phenobarbital produced a dose-dependent protective effect against seizures. The ED50 value of phenobarbital was 2.61 (95 % confidence limits: 1.59 - 4.26) mg . kg-1. Likewise, the ED50 value of allopregnanolone was 0.11 (0.06 - 0.18) mg . kg-1. The combination of allopregnanolone and phenobarbital (1:20) resulted in an ED50 value of 0.73 (0.44 - 1.21) mg . kg-1 with the Q value smaller than 1. In measuring the enhancement of [3H]flunitrazepam binding, we found that the pattern for the concentration-effect curves of phenobarbital with or without allopregnanolone was consistent with that of the theoretical curves of functional synergism.


CONCLUSIONS
There was a synergism between allopregnanolone and phenobarbital for the protective activity against seizures. Also there was a functional synergism between these two agents for the enhancement of [3H]flunitrazepam binding to the GABAA receptor complex in the brain.
Lu
Y Q
YQ
Department of Pharmacology, Medical Center, Fudan University, Shanghai 200032, China.
Yu
R
R
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000378:metabolism; D004357:Drug Synergism; D004597:Electroshock; D005445:Flunitrazepam / Q000378:metabolism; D018757:GABA Modulators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010634:Phenobarbital / Q000627:therapeutic use*; D011280:Pregnanolone / Q000627:therapeutic use*; D012640:Seizures / Q000517:prevention & control*
D000927:Anticonvulsants; D018757:GABA Modulators; D005445:Flunitrazepam; D011280:Pregnanolone; D010634:Phenobarbital