Fig. 8. A schematic diagram illustrating the interaction between dexmedetomidine (represented in black ) and nitrous oxide (N²O; represented in gray ). (A ) In the pretolerant state, dexmedetomidine and nitrous oxide largely counteract and hence antagonize each other’s effects supraspinally. The presynaptic α^2Aadrenoceptors (black ) on primary afferent neurons (activated by dexmedetomidine) and postsynaptic α^2Badrenoceptors (gray ) on spinal interneurons (activated by nitrous oxide) act on either side of a synaptic junction to produce synergy expressed in the motor efferent neuron. The combination of antagonism and synergy results in apparent additivity.(B ) In the tolerant state, there is little counteracting effect of nitrous oxide on the action of dexmedetomidine at the locus ceruleus; hence, only the synergistic interaction at the level of the spinal cord is observed when the drugs are used in combination. α^2A= A subtype of α²adrenergic receptor; α^2B= B subtype of α²adrenergic receptor; PAG = periaqueductal gray region; Dex = dexmedetomidine, a selective α²adrenoceptor agonist; NE = norepinephrine.