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Dextromethorphan (DEX) presynaptically decreases glutamatergic transmission in second-order neurons of the nucleus tractus solitarius (TS). To clarify the inhibitory mechanism of DEX, the present study examined the interaction of DEX with cAMP. The effects of DEX on miniature and TS-evoked excitatory postsynaptic currents (mEPSCs and eEPSCs) were recorded under activation of the cAMP-dependent pathway using the brainstem slices. An increase in cAMP by forskolin counteracted the inhibitory effect of DEX on mEPSCs. Eight-Bromo-cAMP and N-ethylmaleimide also attenuated the DEX effect. However, forskolin had negligible effects on the DEX-induced inhibition of eEPSCs. This suggests that DEX decreases spontaneous glutamate release by inhibiting the cAMP-dependent pathway and synchronous release by another unknown mechanism.
This article was published in the following journal.
Resveratrol is a natural non-flavonoid polyphenol found in red wine, which has numerous pharmacological properties including anti-stress and antidepressant-like abilities. However, whether the antidep...
Rho-kinase activity is a key regulator in the maintenance of corporal vasoconstriction and penile detumescense. Also, importance of l-cysteine/HS pathway in erectile tissue has been shown; however it ...
Fluoxetine (FLX), a widely used antidepressant primarily acting as a selective serotonin reuptake inhibitor (SSRI), has been shown to exhibit other mechanisms of action in various cell types. Conseque...
We previously reported that sevoflurane-induced pica, kaolin ingestion behavior, in rats has the potential to reflect post-operative nausea and vomiting (PONV) in humans. It is well-known that cortico...
Zinc pyrithione (ZPT), a zinc coordination complex, is used as an antimicrobial agent. This study investigated the molecular mechanisms underlying ZPT-induced spermatozoa immobilization by examining p...
A study to study the potential effect of PF-00299804 inhibition of CYP2D6 on dextromethorphan.
The purpose of this study is to determine if addition of dextromethorphan to a stable dose of methadone in opioid dependent subjects will significantly affect physical and psychological as...
This study will assess transcranial magnetic stimulation (TMS) as a biomarker and characterize TMS readouts of the activity of MK2637 and dextromethorphan. Resting quantitative electroence...
In the proposed study, we will build upon our previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspect...
This drug-drug interaction study is being conducted to evaluate the potential effect of Dimebon on the pharmacokinetics on dextromethorphan, a probe substrate of the cytochrome P450 2D6 (C...
A type I cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIBETA SUBUNIT.
A type II cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a higher affinity for cAMP than that of the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIIBETA SUBUNIT. Binding of this subunit by A KINASE ANCHOR PROTEINS may play a role in the cellular localization of type II protein kinase A.
A type II cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIIALPHA SUBUNIT. Binding of this subunit by A KINASE ANCHOR PROTEINS may play a role in the cellular localization of type II protein kinase A.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
Methyl analog of DEXTRORPHAN that shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (RECEPTORS, N-METHYL-D-ASPARTATE) and acts as a non-competitive channel blocker. It is one of the widely used ANTITUSSIVES, and is also used to study the involvement of glutamate receptors in neurotoxicity.