title: Propofol combined with diazepam synergistically potentiates the GABA-activated chloride current in rat sensory neurons.
abstract: OBJECTIVE
  To investigate the effect of propofol combined with diazepam on the gamma-aminobutyric acid (GABA)-activated chloride current (IGABA) evoked in rat sensory neurons.
  
  
  METHODS
  Whole cell patch clamp recordings were made from cultured rat dorsal root ganglionic neurons. GABA (3 mumol/L) was applied by pressure ejection. The anesthetics were dissolved in the external solution and given by the "Y-tube" method.
  
  
  RESULTS
  Co-application of propofol (0.3-3 mumol/L) and diazepam (100 nmol/L) potentiated the IGABA which was significantly larger than the sum of that potentiated by drug alone. Diazepam (100 nmol/L) shifted the concentration-response curve for the IGABA potentiation induced by propofol to the left in a parallel fashion. The EC50 value for propofol was decreased by diazepam from 7.6 +/- 1.8 mumol/L to 3.9 +/- 1.1 mumol/L (n = 9).
  
  
  CONCLUSIONS
  Our results suggest that propofol combined with diazepam synergistically potentiates the IGABA. Diazepam-induced increase in the apparent binding affinity of propofol for the GABAA receptors is likely responsible for a clinical synergistic hypnotic action during co-application with propofol and diazepam.
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical University, Wuhan 430030, China.
authors.forename: A
authors.initials: A
authors.lastname: Luo
authors.forename: K
authors.initials: K
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D018118:Chloride Channels; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D015742:Propofol