Differential effects of dextrorphan and levorphanol on the excitation of rat spinal neurons by amino acids

Church, John A.; Lodge, David; Berry, Stephen C.

doi:10.1016/0014-2999(85)90755-1

Cited by 145 publications

(51 citation statements)

References 11 publications

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“…Furthermore, it modifies several ligand-gated currents including glycineinduced currents (8) and serotonin-induced inward currents (9). More intriguingly, DEX acts as an antagonist of N-methyl-D-aspartate (NMDA) receptors (10) or as an agonist of σ receptors (11). Drugs having the characteristics of blocking NMDA receptors (12,13) and stimulating σ receptors (14 -16) possess antitussive activity.…”

Section: Introductionmentioning

confidence: 99%

Dextromethorphan Inhibits the Glutamatergic Synaptic Transmission in the Nucleus Tractus Solitarius of Guinea Pigs

2011

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Abstract. 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 secondorder 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.

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Section: Introductionmentioning

confidence: 99%

Dextromethorphan Inhibits the Glutamatergic Synaptic Transmission in the Nucleus Tractus Solitarius of Guinea Pigs

2011

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“…This process occurs in the dorsal horn of the spinal cord, where DM blocks NMDA receptors, reducing the threshold for pain transmission via the Aδ-and C-sensory fibers (85). The activation of neuronal firing by NMDA receptors increases intracellular calcium levels (86). DM has been shown to reduce and regulate the influx of intracellular calcium through NMDA receptor-gated channels (87), thereby antagonizing the effects of excitatory amino acids and reducing the release of various peptides, such as glutamate and aspartate.…”

Section: Effects On Pain Sensationmentioning

confidence: 99%

Neuropsychotoxic and Neuroprotective Potentials of Dextromethorphan and Its Analogs

et al. 2011

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Abstract. Dextromethorphan (3-methoxy-17-methylmorphinan) has complex pharmacologic effects on the central nervous system. Although some of these effects are neuropsychotoxic, this review focuses on the neuroprotective effects of dextromethorphan and its analogs. Some of these analogs, particularly dimemorfan (3-methyl-17-methylmorphinan) and 3-hydroxymorphinan, have promising neuroprotective properties with negligible neuropsychotoxic effects. Their neuroprotective effects, the mechanisms underlying these effects, and their therapeutic potential for the treatment of diverse neurodegenerative disorders are discussed.

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“…3,4) Dextrorphan has been shown to act as an antagonist of the excitatory neurotransmitter N-methyl-D-aspartate (NMDA), 5) being more potent than dextromethorphan. 6,7) It has thus been suggested that the effect of dextromethorphan may be due to conversion to dextrorphan. 8) An interesting issue is whether dextrorphan is subjected to further metabolism in the body.…”

mentioning

confidence: 99%

Human Cytosolic Sulfotransferase SULT1A3 Mediates the Sulfation of Dextrorphan

Yamamoto

Kurogi

Schiefer

et al. 2016

Biological & Pharmaceutical Bulletin

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Dextrorphan, an active metabolite of the antitussive dextromethorphan, has been shown to be subjected to sulfation by several zebrafish cytosolic sulfotransferases (SULTs). We were interested in finding out which of the human SULT(s) is(are) capable of catalyzing the sulfation of dextrorphan, and to verify whether sulfation of dextrorphan may occur in cultured human cells and human organ cytosols. Data from the enzymatic assays showed that, of all thirteen known human SULTs, SULT1A3 displayed the strongest dextrorphansulfating activity. Cell culture experiments using HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells incubated with [35 S]sulfate together with varying concentrations of dextrorphan revealed indeed the production and release of [35 S]sulfated dextrorphan in a concentration-dependent manner. Additionally, significant dextrorphan-sulfating activity was detected in human liver, small intestine and lung cytosols. Taken together, these results provided a biochemical basis for the sulfation of dextrorphan in humans.

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Differential effects of dextrorphan and levorphanol on the excitation of rat spinal neurons by amino acids

Cited by 145 publications

References 11 publications

Dextromethorphan Inhibits the Glutamatergic Synaptic Transmission in the Nucleus Tractus Solitarius of Guinea Pigs

Dextromethorphan Inhibits the Glutamatergic Synaptic Transmission in the Nucleus Tractus Solitarius of Guinea Pigs

Neuropsychotoxic and Neuroprotective Potentials of Dextromethorphan and Its Analogs

Human Cytosolic Sulfotransferase SULT1A3 Mediates the Sulfation of Dextrorphan

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