The anesthetic interaction between adenosine triphosphate and N-methyl-D-aspartate receptor antagonists in the rat

Modulation of synaptic neurotransmission through the Ligand-gated ion chann el is probably involved in the mechanisms of analgesic and anesthetic actio ns. In the central nervous system, adenosine triphosphate and glutamate are fast excitatory neurotransmitters through their effects on P2X and N-methy l-D-aspartate (NMDA) receptors respectively. To examine the anesthetic inte raction between adenosine triphosphate and NMDA receptor antagonists, we st udied the effect of intracerebroventricular administration of P2 and/or NMD A antagonists on the minimum alveolar concentration (MAC) of sevoflurane in rats. Intracerebroventricular administration of phosphonopentanoic acid az ophenyl-2',4'-disuIfonate and D (-)-2-anino-5-phophonopentanoic acid, P2 an d NMDA antagonists, significantly reduced the MAC of sevoflurane. The reduc tion of the MAC by both phosphonopentanoic acid azophenyl-2',4'-disulfonate and D (-)-2-anino-5-phophonopentanoic acid was dose-dependent. The effect of coadministration of both antagonists was additive in the reduction of se voflurane minimum alveolar concentration. These results suggest that P2 and NMDA receptors mediate nociceptive/anesthetic processing as inhibition of these receptors resulted in analgesic and anesthetic effects. However the p athway mediated through each receptor may be different postsynaptically and /or one of these presynaptic receptors may modulate the neurotransmitter re lease of the other.