Dextromethorphan inhibits the glutamatergic synaptic transmission in the nucleus tractus solitarius of Guinea pigs

Dextromethorphan (dex) is a widely used non-opioid antitussive. however,the precise site of action and its mechanism were not fully understood. we examined the effects of dex on ampa receptor-mediated glutamatergic transmission in the nucleus tractus solitarius (nts) of guinea pigs. excitatory postsynaptic currents (evoked epscs: eepscs) were evoked in the second-order neurons by electrical stimulation of the tractus solitarius. dex reversibly decreased the eepsc amplitude in a concentration-dependent manner. the dex-induced inhibition of eepsc was accompanied by an increased paired-pulse ratio. miniature epscs (mepscs) were also recorded in the presence of cd 2+ or tetrodotoxin. dex decreased the frequency of mepscs without affecting their amplitude. topically applied ampa provoked an inward current in the neurons,which was unchanged during the perfusion of dex. bd1047,a σ-1-receptor antagonist,did not block the inhibitory effect of dex on the eepscs,but antagonized the inhibition of eepscs induced by skf-10047,a σ-1 agonist. haloperidol,a σ-1 and -2 receptor ligand,had no influence on the inhibitory action of dex. these results suggest that dex inhibits glutamate release from the presynaptic terminals projecting to the second-order nts neurons,but this effect of dex is not mediated by the activation of σ receptors. © the japanese pharmacological society.