Modulatory effects of barbiturates and their binary combinations on human alpha-1 glycine receptors expressed in Xenopus Oocytes

To test whether there is a common site of action for intravenous anaesthetics at the glycine receptor, the effects of binary combinations of thiopentone, pentobarbitone, and methohexitone have been tested on human α1 glycine receptors expressed in Xenopus laevis oocytes using two-electrode voltage-clamp techniques. During this interventional study, recombinant human alpha-1 receptor gene was prepared and the mRNA was injected into cytoplasmic site of Xenopus oocytes. Two-electrod voltage clamp technique used for pharmacological studies of currents of chloride channels (receptors) from the membrane of oocytes. Then, the effect of three barbiturates on currents induced by agonist on the receptors was measured. Thiopentone (5-40mM), and pentobarbitone (25-400mM), (but not methohexitone) potentiated the glycine-induced (50mM) current in a dose-dependent manner, with the maximum potentiation observed to be 220%, and 400%, respectively. In binary combination with thiopentone, or pentobarbitone, methohexitone reduced potentiation compared to that by the individual anesthetics to 180%, and 280%, respectively. Combination of thiopentone and pentobarbitone (50mM) increased potentiation, compared to that by thiopentone alone. Our results indicate that thiopentone and pentobarbitone both act as positive allosteric modulators at the alpha-1 glycine receptor. In contrast, methohexitone has no action alone but acts as a competitive antagonist to thiopentone and pentobarbitone. We suggest that these three intravenous barbiturate anaesthetics share a common site of action at the glycine receptor.