Effect of non-selective gamma-aminobutyric acid receptor stimulation on motor function of the lower oesophageal sphincter and gastro-oesophageal reflux in healthy human subjects.
BACKGROUND
Transient lower oesophageal sphincter relaxation and low lower oesophageal sphincter pressure are the main mechanisms of reflux. It has recently been shown that the stimulation of gamma-aminobutyric acid type B (GABAB) receptors by baclofen decreases the rate of transient lower oesophageal sphincter relaxation and increases the lower oesophageal sphincter pressure in healthy humans. Valproic acid increases synaptosomal GABA concentrations, thus affecting all types of GABA receptors.


OBJECTIVE
To evaluate the effect of valproic acid on transient lower oesophageal sphincter relaxation, lower oesophageal sphincter pressure and gastro-oesophageal reflux.


METHODS
Thirteen healthy subjects underwent 2-h post-prandial oesophageal motility and pH monitoring on two separate occasions after the oral administration of 1 g valproic acid or placebo.


RESULTS
Valproic acid increased the lower oesophageal sphincter pressure by 41% (14.0 +/- 2.1 mmHg vs. 9.9 +/- 2.0 mmHg after placebo, P<0.02), but did not affect the rate of transient lower oesophageal sphincter relaxation (7.9 +/- 1.0/h vs. 8.2 +/- 0.9/h after placebo), the number of reflux episodes or gastro-oesophageal reflux.


CONCLUSIONS
Non-selective GABA receptor stimulation may be beneficial to reflux patients with low lower oesophageal sphincter pressure, but exerts a different modulation of transient lower oesophageal sphincter relaxation than the selective stimulation of GABAB receptors.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003679:Deglutition / Q000187:drug effects; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000502:physiology; D005260:Female; D018682:GABA Agents / Q000494:pharmacology*; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D018079:Receptors, GABA / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology*
D018682:GABA Agents; D018079:Receptors, GABA; D014635:Valproic Acid