title: Synergistic protection of allopregnanolone and phenobarbital against maximal electroshock seizures in mice.
abstract: 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.
authors.affiliation: Department of Pharmacology, Medical Center, Fudan University, Shanghai 200032, China.
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Lu
authors.forename: R
authors.initials: R
authors.lastname: Yu
mesh_terms: 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*
chemical_list: D000927:Anticonvulsants; D018757:GABA Modulators; D005445:Flunitrazepam; D011280:Pregnanolone; D010634:Phenobarbital