Background: Peripheral glucocorticoid receptors (GRs) are altered by peripheral nerve injury and may modulate the development of neuropathic pain. Two central pathogenic mechanisms underlying neuropathic pain are neuroinfl ammation and N-methyl-Daspartate receptor (NMDAR)-dependent neural plasticity in the spinal cord. Objectives: This study examined the eff ect of the non-competitive NMDAR antagonist Dextromethorphan on partial sciatic nerve ligation (PSL)-induced neuropathic pain and the spinal expression of the glucocorticoid receptor (GR). Methods: Male mice were randomly assigned into a sham group and two groups receiving PSL followed by intrathecal saline vehicle or Dextromethorphan (iDMP). Vehicle or iDMP was administered 8-14 days after PSL. The hotplate paw-withdrawal latency was considered to measure thermal pain sensitivity. The spinal cord was then sectioned and immunostained for GR. Results: Thermal hyperalgesia developed similarly in the vehicle and iDMP groups prior to the injections (P = 0. 828 and 0. 643); however, it was completely mitigated during the iDMP treatment (P < 0. 001). GR expression was signifi cantly higher in the vehicle group (55. 64  4. 50) than in the other groups (P < 0. 001). The iDMP group (9. 99  0. 66) showed signifi cantly higher GR expression than the sham group (6. 30  1. 96) (P = 0. 043). Conclusions: The suppression of PLS-induced thermal hyperalgesia by iDMP is associated with the downregulation of GR in the spinal cord, suggesting that this analgesic eff ect is mediated by inhibiting GR-regulated neuroinfl ammation.

Background: CYP2D6 is polymorphically expressed enzyme that show marked interindividual and interethnic variation. Phenotyping of CYP2D6 provides valuable information about real-time activity of this important drug-metabolizing enzymes through the use of specific probe drugs. The aim of this study was to identify the CYP2D6 oxidation phenotype with Dextromethorphan (DEX) as a probe drug in Mazandarani ethnic group among Iranian population. Methods: The study included 71 unrelated healthy volunteers. Dextromethorphan Hydrobromide (30 mg) was given orally to healthy subjects and peripheral venous blood samples (10 ml) were taken at 3 hr post-dose. Dextromethorphan and the metabolite dextrorphan (DOR) were analyzed by the HPLC method.  The log DEX/DOR metabolic ratio (MR) at 3 hr plasma sample was used as the index of CYP2D6 activity and a value of 0.3 was used as the antimode separating extensive metabolizers (EM) and poor metabolizers (PM) phenotypes. Results: A 560-fold interindividual variation in Dextromethorphan MRs was observed in this study. Considering the antimode 0.3 in log scale, 7.04% (5/71) volunteers were identified as PMs.Conclusion: The result showed that the frequency of CYP2D6 PM phenotypes accounted for 7.04% of subjects in our samples. Despite these findings, we propose a further study in larger samples to provide a wider image and to get more valuable information upon pharmacogenetic basis for individual therapy and personalized medicine.

Background: Dextromethorphan (DM) as a non-opioid anti-cough has neuroprotective effects. Combination of DM with quinidine decreases rapid metabolism of DM to dextrorphan (DX). This study aimed to examine the effects of acute administration of quinidine, DM and combination of Dextromethorphan/quinidine (DM/Q) on pentylenetetrazole (PTZ)-induced clonic and tonic seizure thresholds in mice. Materials and Methods: A total of 84 male mice of the NMRI strain (20-25 g, n=7 in each group) were used in this study. Different doses of DM (5, 10, 25 and 50 mg/kg), quinidine (10, 20, and 30 mg/kg) and DM/Q (5/20, 10/20, 25/20, and 50/20 mg/kg) were intraperitoneally administrated 30 min before the seizure induction. Intravenous infusion of PTZ was used to induce seizure induction and latencies to the occurrence of general clonus and tonic hind limb extension were recorded and converted to the seizure threshold dose. Results: Quinidine at a dose of 30 mg/kg significantly increased the threshold of tonic seizure (P<0. 05). DM at doses of 25 and 50 mg/kg significantly increased threshold of clonic (P<0. 05) and tonic (P<0. 001) seizures. DM/Q at dose of 50/20 mg/kg significantly decreased the threshold of clonic and tonic seizures (P<0. 001). Conclusion: According to the findings of this study, different effects of DM on clonic and tonic seizure thresholds may represent different sensitivities of forebrain and hindbrain seizure circuitry to DM. Also, decreased effect of DM in the presence of quinidine may also be due to a change in the metabolism of DM.

Background: Intra-operative pain has adverse effects on hemodynamic parameters. Due to complications of opioids for pain relief, using non-opioids medication is preferred. The purpose of this study was to investigate the effect of oral dextrometorphan premedication on intra-operative Morphine requirement. Methods: After approval of the Ethics committee and informed consent, 40 adult patients who stand in American Society of Anesthesiologists Physical Status I and II, under general anesthesia for elective laparatomy were selected and classified in two equal groups randomly. In group A, oral Dextromethorphan (60mg) was administered at 10 PM and 6 AM preoperatively. In group B, placebo (dextrose) was administered. After induction of general anesthesia and before skin incision, intravenous morphine (0.01 mg/kg) was administered. During surgery, when systolic blood pressure or heart rate was increased more than 20% of the preoperative baseline, 0.01 mg/kg morphine was administered. At the end of surgery, the totally prescribed morphine (mg/kg) and maximal increase in systolic, diastolic, mean arterial blood pressure and heart rate relative to the baseline values were calculated and statistically compared with student’s t-test. Results: The mean dose of administered morphine during surgery was significantly less in group A than group B (P<0.0001). Also, Maximal increase in systolic, diastolic and mean arterial blood pressure was significantly less in group A (p<0.003, p<0.004, p<0.0001, respectively). There was no significant difference in maximal heart rate increase between two groups (p<0.114). Conclusion: Oral Dextromethorphan premedication may decrease intra-operative morphine requirement and reduce maximal increase in systolic and mean arterial blood pressure during surgery.  

a-Bromoketals and acetals are important synthetic precursors in organic synthesis. In this work, some new α-bromoketals are synthesized by the reaction of aryl methyl ketones with diols in the presence of 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) Hydrobromide-perbromide in good isolated yields. The latter compound converts aldehydes to acetals and serves as a new and efficient reagent for the synthesis of acetals. Comparative studies of the preparation of a-bromoketal and acetals using some reported methods versus the present method show that DBUH-Br3 is one of the most efficient reagents for the preparation of these compounds. Conversion of carbonyl compounds to corresponding a-bromoketals and acetals in the presence of DBUH-Br3 under microwave irradiation is also described.

Background and purpose: Cyclosporine (Cyc) is a calcineurin inhibitor used in immunosuppressive therapy that may cause psychological problems such as depression. Previous investigations have shown the positive antidepressant effects of Dextromethorphan (Dxt). Therefore, the aim of this study was the evaluation of the Dxt effect on Cyc-induced depression in an animal model of despair in two separate cohorts. Experimental approach: Male albino mice were used, first total activity was evaluated by the locomotor test, and then after that, the immobility time during the forced swimming test was measured as an indicator of depression. Cyc, Dxt, and fluoxetine (the reference antidepressant drug) were all administered IP. Tests were performed either 4 h after injection (cohort 4 h) or in separate groups 24 h after injection (cohort 24 h). Findings/Results: Cyc reduced total activity measured after 4 h in the locomotor test and it was normalized after 24 h. Immobility time dose-dependently increased during the forced swimming test and remained so after 24 h (cohort 24 h; Cyc 10, 20, and 40 mg/kg, 157 ± 22, 180 ± 8, and 228 ± 4 s, respectively; Cyc 40 mg/kg P < 0. 001 vs control 142 ± 13 s) that indicated Cyc induced depressive-like behavior. Dxt (30 mg/kg) like fluoxetine reduced the immobility time when co-administered with Cyc compared with Cyc and remained effective after 24 h (cohort 24 h; 120 ± 30, P < 0. 001 vs Cyc 40 mg/kg alone). Conclusion and implications: Dxt was a useful drug for preventing Cyc-induced depression that remained effective for 24 h in mice. Since interpretation from animal studies to humans must be done with caution further clinical studies on the effect of Dxt in patients suffering from psychological side effects of Cyc may be reasonable.

BACKGROUND AND OBJECTIVE: Dextromethorphan is a NMDA receptor antagonist in the glutamatergic system. Currently, there are reports showing that the glutamatergic NMDA receptor mechanism stimulates dopamine release from several brain regions. This effect may modulate the stereotyped behaviors of dopaminergic system. The purpose of this study was to determine the interaction between Dextromethorphan and stereotyped licking behavior in rats. In the present study, effects of Dextromethorphan and different dopamine receptor antagonists on apomorphine-induced licking behavior were examined.METHODS: For the induction of licking, the dose of 0.5 mg/kg, s,c. of apomorphine was used. FINDINGS: Dextromethorphan (10-30 mg/kg, i.p.) dependently reduced the licking behavior. Intraperitoneal injection of Dextromethorphan (15 mg/kg, ED50) potentiated the inhibitory effects of low doses of the dopamine D1 receptor antagonist, SCH 23390 (0.00625 and 0.0125 mg/kg, i.p.) and the dopamine D2 receptor antagonist, pimozide (0.5-1 mg/kg, i.p).CONCLUSIONT: these results suggest that the inhibitory effect of Dextromethorphan on apomorphine induced licking behavior is mediated via a dopamine D1 receptor mechanism.

Introduction: We describe a patient scheduled for elective surgery who regularly consumed approximately 12 to 15 times the maximum recommended daily dose of Dextromethorphan. We describe the clinical pharmacology of Dextromethorphan and discuss its anesthetic implications.Case Presentation: A 30-year-old man with a history of a nasal fracture was scheduled to undergo an elective septorhinoplasty. He reported daily consumption of large quantities (1440 to 1800 mg) of Dextromethorphan for six years. He was previously treated for Dextromethorphan dependency on several occasions with urine Dextromethorphan levels exceeding 2000 ng/mL. He described marked dissociative effects when abusing the drug, but had abstained from use for 48 hours before his elective surgery. Considering that Dextromethorphan has a relatively short half-life and that the patient did not suffer major withdrawal symptoms after voluntarily discontinuing the drug, the authors proceeded with the case while recognizing that the drug has significant neuropsychiatric and sympathetic nervous system stimulant effects resulting from its actions as a N-methyl-D-aspartate receptor antagonist.Conclusions: Anesthesiologists need to be aware of Dextromethorphan’s clinical pharmacology because recreational abuse of the drug has become increasingly common in adolescents and young adults.