Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dextromethorphan”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1997

Interaction between dextromethorphan and norpethidine in rats.

With increasing interest in the application of dextromethorphan in pain control, it is probable that patients will receive this drug in combination with analgesics such as opioids, giving rise to the potential for previously unobserved drug interactions. The interaction between dextromethorphan, and its pharmacologically active metabolite dextrorphan, and norpethidine, a toxic metabolite of pethidine, was examined in rats. Rats were assigned to receive dextromethorphan (0, 20 or 40 mg/kg) or dextrorphan (0, 15 or 30 mg/kg) combined with norpethidine (0, 28 or 42 mg/kg). The occurrence of seizures, myoclonic jerks and shivering was recorded for 60 min after drug administration. Norpethidine produced dose-related increases in the incidence of seizures, myoclonic jerks and shivering. Dextromethorphan, but not dextrorphan, increased the incidence of these behaviours. It is recommended that extreme caution be exercised if dextromethorphan and pethidine are to be used together.

Journal Article↗
PubMed1988

Simultaneous determination of pseudoephedrine hydrochloride, chlorpheniramine maleate, and dextromethorphan hydrobromide by second-derivative photodiode array spectroscopy.

The simultaneous determination of the active ingredients in multicomponent pharmaceutical products normally requires the use of a separation technique, such as HPLC or GC, followed by quantitation. Presented here is a rapid, validated, analytical method that does not require prior separation for the simultaneous determination of three drugs, pseudoephedrine hydrochloride, chlorpheniramine maleate, and dextromethorphan hydrobromide, in a tablet formulation. A diode array spectrophotometer, capable of multicomponent analysis, was used for the quantitation. The utility of this method was demonstrated in two ways: the analysis of a chewable pediatric tablet (formulation CP) containing 7.5 mg of pseudoephedrine hydrochloride, 0.5 mg of chlorpheniramine maleate, and 2.5 mg of dextromethorphan hydrobromide, and the dissolution analysis of a hydroxypropyl methylcellulose-based sustained-release tablet (formulation SR) containing 120 mg of pseudoephedrine hydrochloride, 8 mg of chlorpheniramine maleate, and 60 mg of dextromethorphan hydrobromide. The sensitivity of this assay is 7.5 micrograms/mL for pseudoephedrine hydrochloride, 1.0 micrograms/mL for chlorpheniramine maleate, and 5.0 micrograms/mL for dextromethorphan hydrobromide, using the second-derivative spectra of the absorbance with respect to wavelength. Determinations were made in 0.1 M sodium acetate buffer at pH 5.0 using a 1-cm quartz cell. Absorbance spectra, and their first and second derivatives, from 240 to 300 nm were used for the determination. The results obtained by this method compared favorably with the results obtained by a validated HPLC method.

Chlorpheniramine↗
PubMed2000

Premedication with dextromethorphan provides posthemorrhoidectomy pain relief.

PURPOSE: Previous studies have shown that N-methyl-D-aspartate receptor antagonists provide a preemptive analgesic effect in humans. This study was designed to examine whether premedication with dextromethorphan, an N-methyl-D-aspartate antagonist, also provided a preemptive analgesic effect that improved postoperative pain management. METHODS: Sixty patients who were American Society of Anesthesiologists status I and II scheduled for hemorrhoidectomy (modified Whitehead procedure) were included in the study. Patients were randomly assigned to the control and study groups. For the control group patients received chlorpheniramine maleate (20 mg), a component of the injection form of dextromethorphan, intramuscular injection 30 minutes before skin incision. In the study group dextromethorphan 40 mg containing 20 mg chlorpheniramine maleate (intramuscular) was given as premedication 30 minutes before skin incision. Pethidine (1 mg/kg, intramuscular) was given for pain relief as required postoperatively. The time to first pethidine injection, total pethidine consumption, worst pain score, and pethidine-related side effects were recorded for 48 hours postoperatively. RESULTS: The times to first pethidine injection (mean +/- standard error of the mean) were 5.2 +/- 3 and 19.6 +/- 6 hours in the control and study groups, respectively. Total pethidine consumption was 140 +/- 11.3 and 63.5 +/- 11.8 mg in the control and study groups. The worst visual analog scale pain scores were 7.4 +/- 0.2 and 5.6 +/- 0.3 in the control and study groups during the two-day observation. The numbers of patients who required pethidine injection were 29 and 20 in the control and study groups, respectively. Two patients suffered pethidine-related side effects, such as nausea, vomiting, dizziness, and headache, in the control group, and no patient complained of any side effect in the study group. CONCLUSION: We found that dextromethorphan premedication provided a preemptive analgesic effect, thus producing reduced postoperative pain and pethidine requirement and improved recovery from hemorrhoidectomy.

Adult↗
PubMed2000

Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice.

The tail-flick test was used to investigate the effects of chronic administration of the N-methyl-D-aspartate (NMDA) receptor antagonists, dextromethorphan, memantine and MRZ 2/579, on the development and reversal of morphine tolerance in mice in three separate experiments. Experiment 1 investigated the effects of NMDA receptor antagonists on the development of tolerance. Morphine (10 mg/kg for 6 days, twice daily) produced a 5.9-fold rightward shift of the cumulative dose-response curves. Co-administration of dextromethorphan, memantine or MRZ 2/579 between tests 1 and 2 dose-dependently (5-10 mg/kg) inhibited the development of morphine tolerance. In experiment 2, in which the effects on the reversal were investigated, morphine-tolerant mice were treated b.i.d. for an additional 6 days (between tests 2 and 3) with vehicle+vehicle, NMDA receptor antagonist+vehicle, vehicle+morphine or NMDA receptor antagonist+morphine. Morphine-tolerant mice treated with vehicle+vehicle remained morphine tolerant, whereas this residual morphine tolerance was inhibited by administration of all three NMDA antagonists (each 10 mg/kg). Morphine-tolerant mice receiving vehicle+morphine injections demonstrated an unchanged degree of antinociceptive tolerance. In these mice, the co-administration of memantine and MRZ 2/579, but not dextromethorphan, resulted in the reversal of morphine tolerance. In experiment 3, memantine and MRZ 2/579 (10 mg/kg) inhibited the acute antinociceptive effect of morphine, but dextromethorphan did not. These data indicate that low-affinity, clinically available and/or therapeutically promising NMDA receptor antagonists may be used to inhibit ongoing morphine tolerance.

Analgesics, Opioid↗
PubMed2001

Effects of methylprednisolone and dextromethorphan on lipid peroxidation in an experimental model of spinal cord injury.

OBJECTIVE: This study examines the effects of agents purported to improve recovery following spinal cord trauma, methylprednisolone sodium succinate, dextromethorphan, and the combination of both, on the post-traumatic alterations of membrane lipid metabolism. METHODS: After sparing ten rats for a control group (G1) and performing T3-T6 laminectomies in 150 rats, spinal cord injuries were accomplished in 120 of 150 Wistar rats with an aneurysmal clip compression at the level of T4-5 for 30 sec. Hence the G2 group ( n 30) included the "only laminectomy/sham" group. The 120 injured animals were subdivided into four equal groups ( n 30 each). Group G3 underwent no therapy, G4 methylprednisolone (MP), G5 dextromethorphan (DM), and G6 MP+DM therapies. Groups G2-G6 were killed ten by ten at 10 min, 30 min, and 120 min after the operation. We measured tissue (MDA) and blood malonyldialdehyde (MDAb), (a product of lipid peroxidation) levels as an indicator of oxidative damage by thiobarbituric acid method and activity levels of antioxidant enzymes superoxide dismutase and glutathione peroxidase in erythrocytes. Intergroup and intragroup results were compared statistically. RESULTS: Methylprednisolone was able to keep the levels for all parameters close to baseline except for 30-min MDA, MDA(b), and SOD values. But their results were all different from those of G3. Dextromethorphan was successful in this respect at 30-min GSH-Px and 120-min SOD and GSH-Px, and all values were also different from G3 values except for 10-min MDA, SOD, and GSH-Px. Combined therapy was not able to keep levels close to baseline for all parameters, but they were different from G3's except for the GSH-Px values. Methylprednisolone values displayed minimal alterations according to baseline at 120 min. Dextromethorphan was relatively unsuccessful at 10 min. Combined therapy did not show benefit superior to MP/DM single therapies.

Animals↗
PubMed1987

High-performance liquid chromatographic assays for bufuralol 1'-hydroxylase, debrisoquine 4-hydroxylase, and dextromethorphan O-demethylase in microsomes and purified cytochrome P-450 isozymes of human liver.

Bufuralol, debrisoquine, and dextromethorphan are three prototype substrates of the common genetic deficiency of oxidative drug metabolism in man known as debrisoquine/sparteine-type polymorphism. We describe assays for the in vitro metabolism of (+)- and (-)-bufuralol, debrisoquine, and dextromethorphan in human liver microsomes and reconstituted purified cytochrome P-450 isozymes. These assays combine nonextractive sample preparation by precipitation of protein with perchloric acid with reversed-phase inorganic ion-pair HPLC and fluorescence detection. The minimal detectable levels of the major metabolites formed are 1'-hydroxybufuralol, 0.1 ng/ml; 4-hydroxydebrisoquine, 0.8 ng/ml; and dextrorphan, 0.1 ng/ml. Formation of these metabolites is linear for at least 45 min and between 1 and 100 micrograms of microsomal protein. Comparative kinetic analysis of the three monooxygenase reactions in human liver microsomes revealed an apparent biphasicity of (+)- and (-)-bufuralol 1'-hydroxylation and dextromethorphan O-demethylation but monophasic formation of 4-hydroxydebrisoquine in the substrate concentration range (less than 1 mM) studied. These data, in combination with those obtained by purified human cytochrome P-450 isozymes indicate the involvement of the same enzyme in the metabolism of all three substrates investigated. However, additional and distinct activities contribute to the metabolism of (+)- and (-)-bufuralol and dextromethorphan.

Chromatography, High Pressure Liquid↗
PubMed1990

Inhibitory studies of mexiletine and dextromethorphan oxidation in human liver microsomes.

The cytochrome P-450dbl isozyme (P-450bdl) is responsible for the genetic sparteine-debrisoquine type polymorphism of drug oxidation in humans. To investigate the relationship between mexiletine oxidation and the activity of this isozyme, cross-inhibition studies were performed in human liver microsomes with mexiletine and dextromethorphan, a prototype substrate for P-450dbl. The formation of hydroxymethylmexiletine and p-hydroxymexiletine, two major mexiletine metabolites, was competitively inhibited by dextromethorphan. Mexiletine competitively inhibited the high affinity component of dextromethorphan O-demethylation. In addition, there was a good agreement between the apparent Km values for the formation of both mexiletine metabolites and the high affinity component of dextromethorphan O-demethylation and their respective apparent Ki values. Several drugs were tested for their ability to inhibit mexiletine oxidation. Quinidine, quinine, propafenone, oxprenolol, propranolol, ajmaline, desipramine, imipramine, chlorpromazine and amitryptiline were competitive inhibitors for the formation of hydroxymethylmexiletine and p-hydroxymexiletine as for prototype reactions of the sparteine-debrisoquine type polymorphism. Amobarbital, valproic acid, ethosuximide, caffeine, theophylline, disopyramide and phenytoin, known to be non-inhibitors of P-450dbl activity, were found not to inhibit the formation of these mexiletine metabolites. Moreover, the formation of both metabolites was strongly inhibited by an antiserum containing anti-liver/kidney microsomes antibodies type I (anti-LKMI) directed against P-450dbl. These data suggest that the formation of two major metabolites of mexiletine is predominantly catalysed by the genetically variable human liver P-450dbl.

Binding, Competitive↗
PubMed1991

Dextromethorphan protects against the neurotoxic effects of p-chloroamphetamine in rats.

Dextromethorphan, an agent that blocks the neuronal-damaging effects of hypoxemia in vitro, was tested for its ability to prevent the neurotoxic effects of p-chloroamphetamine (PCA). Rats were treated with either saline, PCA, dextromethorphan, or the combination of PCA and increasing doses of dextromethorphan. Dextromethorphan provided a dose-related protection against the serotonin (5-HT)-depleting effects of PCA. These observations may offer a clue as to the mechanism responsible for PCA-induced neurotoxicity.

Animals↗
PubMed1988

GC and GC-MS procedures for simultaneous phenotyping with dextromethorphan and mephenytoin.

A genetic deficiency in the metabolism of dextromethorphan and mephenytoin may be revealed by the excretion pattern of dextromethorphan and its metabolite dextrorphan, and mephenytoin, 4-OH-mephenytoin, respectively, after a single dose of the test drugs. Existing methods were modified for determining the compounds in 0.1-0.5 ml urine samples. No prior derivatization of the compounds was necessary before their gaschromatographic or mass-spectrometric analysis by using crosslinked 5% phenylmethyl silicone fused silica columns. Seven healthy volunteers were phenotyped at weekly intervals with either 25 mg dextromethorphan or 100 mg mephenytoin, or both drugs. One subject was a poor metabolizer of mephenytoin, while all subjects were extensive metabolizers of dextromethorphan. Neither a pharmacokinetic nor an analytical interference was observed when the results of the single test were compared with those of the combined test. The results of the mephenytoin test were also tentatively given in form of metabolic ratios. The GC-MS assay was designed for clinical studies so that patients treated with other drugs could be phenotyped.

Adult↗
PubMed1993

Dextromethorphan blocks N-methyl-D-aspartate-induced currents and voltage-operated inward currents in cultured cortical neurons.

The effect of dextromethorphan on several types of cation currents in cultured rat cortical neurons and PC12 cells was studied by using the whole-cell configuration of the patch-clamp technique. The Ba2+ current through L- and N-type Ca2+ channels was blocked with similar potencies (52-71 microM) in both types of cells. The effect was not voltage-dependent, in contrast to that of amlodipine (a dihydropyridine). Dextromethorphan was able to block the Ba2+ current completely unlike amlodipine and omega-conotoxin (an N-type channel blocker) which produced only partial inhibition. The voltage-activated Na+ and Ca2+ channels in cortical neurons were inhibited by similar concentrations of dextromethorphan (IC50 approximately 80 microM). The morphinan was at least 100 times more potent (IC50 = 0.55 microM) as a blocker of the current induced by N-methyl-D-aspartate (NMDA) in cortical neurons. Currents induced by (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ((RS)-AMPA) or kainic acid were not significantly affected even at 1 mM. The results suggest that the neuroprotective effect of dextromethorphan, previously found to occur in a concentration range of 10-100 microM, may be due to a complete blockade of the NMDA receptor channel and a partial inhibition of voltage-dependent Ca2+ and Na+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Adverse effects of dextromethorphan on the spatial learning of rats in the Morris water maze.

The effects of the non-competitive NMDA receptor antagonist dextromethorphan on spatial learning were assessed using the Morris water maze. Dextromethorphan was administered to 4 groups of rats in 10, 20, 30, and 40 mg/kg doses. An additional group of rats was administered saline to serve as a vehicle control group. Dextromethorphan impaired learning dose dependently in the initial training phase of the experiment. During the probe trial, dose-dependent performance deficits were noted in the first 15 s of the trial only. Search strategy differences between the lowest and highest dose groups were also observed during the probe trial. During the reversal training phase, when the platform was moved to a new location, the dose-dependent impairment was seen again, but the 40 mg/kg group perseverated to the former location longer than the other groups. A cued control trial indicated that in addition to the learning impairment produced, the highest dose of dextromethorphan may also impair sensory-motor coordination.

Animals↗
PubMed1988

Anticonvulsant effects of dextrorphan in rats: possible involvement in dextromethorphan-induced seizure protection.

The major metabolite of the non-opioid anticonvulsant/antitussive dextromethorphan is dextrorphan. In the present study, the effects of dextrorphan were determined in an experimental model of seizure activity (maximal electroshock convulsions) (MES). Subcutaneous administration of dextrorphan produced dose-related blockade of tonic hindlimb extension (THE) and a decrease in the duration of tonic forelimb extension (TFE). The anticonvulsant effect of dextrorphan was linear and maximally efficacious. Compared to the prototypical anticonvulsant drug diphenylhydantoin, dextrorphan was 2.5 times more potent (ED50's = 30 mumol/kg and 12 mumol/kg, respectively). Pretreatment with naloxone failed to antagonize dextrorphan-induced blockade of THE. Moreover, pretreatment with dextrophan failed to significantly enhance the anticonvulsant potency of diphenylhydantoin. It is likely that the anticonvulsant effects of dextrorphan are related to its actions at the phencyclidine/N-methyl-D-aspartate receptor complex, whereas the anticonvulsant effects of dextromethorphan have been attributed to binding to a specific dextromethorphan site in the brain. Therefore, we suggest that while metabolism to dextrorphan could possibly contribute to the anticonvulsant effects of dextromethorphan, it is probably through an unrelated receptor mechanism.

Animals↗
PubMed1987

Allosteric modulation of dextromethorphan binding sites.

The nonopioid antitussives dextromethorphan (DM), carbetapentane and caramiphen are efficacious anticonvulsant agents in the rat MES test. The findings presented strongly suggest the existence of a novel allosteric mechanism by which drugs acting at two different but interacting sites, exert their effects. This mechanism has marked similarities with the gamma-aminobutyric acid (GABA)-benzodiazepine interactions, even though their binding sites are different. The allosteric interactions of dextromethorphan and phenytoin in the binding assay and the potentiation of the anticonvulsant effects of phenytoin by dextromethorphan suggest that drugs that bind to the dextromethorphan sites could be used to reduce the effective dose of phenytoin and reduce its side effects, at least those which are not an extension of its specific pharmacological actions. It is evident that the investigation of the molecular mechanisms described may help to open new approaches to understand and treat convulsive disorders, to find novel anticonvulsant drugs and to further explain some of the molecular mechanisms of neuronal excitability.

Animals↗
PubMed1991

Dextromethorphan and levorphanol on dorsal horn nociceptive neurones in the rat.

Intrathecal administration of dextromethorphan and levorphanol and intravenous injection of dextromethorphan were tested on the electrophysiological response of deep multireceptive dorsal horn neurones to peripheral stimuli. Both blockade of C-fibre input to the cells and wind-up, the increase in C-fibre firing with repeated stimulus, were recorded. Intrathecal injection of levorphanol (0.25-100 micrograms) had a typical opioid effect, blocking the C-fibre input. Its affect on wind-up was dose-dependent, paralleled precisely the blocking effect on the C-fibre input and both effects were reversed by naloxone. Unlike levorphanol and other opiates, intrathecal administration of dextromethorphan (50-500 micrograms) blocked the C-fibre input and A beta response in parallel and was not reversed by naloxone. Wind-up was reduced by a maximum of 56% at the largest dose tested. Intravenous injection of dextromethorphan (5 mg/kg) also produced a reduction in wind-up but not in the C-fibre response.

Animals↗
PubMed1989

Dextromethorphan and neuromodulation: old drug coughs up new activities.

Dextromethorphan is one of the most widely used non-opioid cough suppressants, representing the active ingredient in several over-the-counter antitussive formulations. It does not possess the CNS pharmacology of other opiates in humans (i.e. analgesia, respiratory depression, abuse liability or psychotomimetic properties), but since the discovery in 1981 of high affinity recognition sites in brain for dextromethorphan a unique neuropharmacological profile has emerged for this relatively innocuous drug. Anticonvulsant and neuroprotective properties have been demonstrated, and treatment with dextromethorphan has been shown to improve the cerebrovascular and functional consequences of global cerebral ischemia. Frank Tortella and colleagues review the CNS pharmacology of dextromethorphan, its possible involvement with NMDA or sigma-receptors, and the potential clinical importance of this old 'new' drug.

Animals↗
PubMed1995

Dextromethorphan suppresses both formalin-induced nociceptive behavior and the formalin-induced increase in spinal cord c-fos mRNA.

The injection of dilute formalin results in a stereotyped nociceptive behavioral response. Administration of dextromethorphan (s.c.) but not saline, 30 min prior to intraplantar formalin injection prevents this nociceptive response in a dose-dependent manner. In addition, intraplantar formalin reliably induces c-fos mRNA in the ipsilateral spinal dorsal horn as assessed with quantitative solution hybridization at 30 min postinjection. No change in c-fos mRNA was detected in the contralateral spinal dorsal horn, nucleus raphe magnus, periaqueductal grey, medial thalamus, or sensorimotor cortex. Pretreatment with dextromethorphan at 60 mg/kg s.c., 30 min prior to formalin resulted in a suppression of c-fos induction, so that c-fos mRNA levels in the ipsilateral spinal dorsal horn of animals receiving dextromethorphan prior to formalin did not differ from controls. These data indicate that dextromethorphan suppresses formalin nociceptive behavior and one of the biochemical consequences of formalin nociception, i.e., induction of c-fos mRNA.

Animals↗
PubMed1994

Dextromethorphan attenuates and reverses analgesic tolerance to morphine.

Tolerance to the antinociceptive (analgesic) effect of morphine, a mu-opioid agonist, was developed in male CD-1 mice as assessed by a shift to the right of the analgesic (tail-flick) dose-response curves and an increase in the ED50 values. Administration of dextromethorphan at 30 mg/kg s.c., but not saline, 30 min prior to an escalating 3 times per day (t.i.d.) morphine dosing schedule prevented a 5-fold increase in the morphine ED50 value observed on treatment day 4. Concurrent administration of dextromethorphan at 12 mg/kg/24 h by s.c. infusion prevented the 6-fold increase in the morphine ED50 value that was observed in control mice that received morphine at 30 mg/kg/24 h by s.c. infusion. Implantation of two 25 mg morphine pellets resulted in a 10-fold increase in the morphine ED50 value on treatment day 4. Administration of dextromethorphan at 30 mg/kg s.c. t.i.d., but not saline, resulted in a reversal of morphine tolerance with the almost complete return of the morphine ED50 value to the control (opioid naive) value. These results demonstrate that dextromethorphan, an NMDA receptor antagonist can modulate morphine (mu-receptor)-mediated tolerance.

Analgesics↗
PubMed1994

Mixed ion pair liquid chromatography method for the simultaneous assay of ascorbic acid, caffeine, chlorpheniramine maleate, dextromethorphan HBr monohydrate and paracetamol in Frenadol sachets.

The five active drug substances and two of the excipients present in Frenadol, a cold medication, were separated. The active drug components dextromethorphan HBr monohydrate, ascorbic acid, caffeine, paracetamol and chlorpheniramine maleate were quantitatively assayed by a mixed ion pair LC method. The excipients separated were citric acid and maleic acid. The HPLC assay included dual-wavelength detection to simultaneously quantify the large concentration of paracetamol and the much lower concentration of chlorpheniramine and dextromethorphan. Both tetrabutylammonium hydrogen sulphate (TBA) and pentane sulphonic acid (PSA) were necessary for resolution of the seven compounds. The TBA was necessary to lessen peak tailing for dextromethorphan and chlorpheniramine, to retain ascorbic acid and to shorten assay time. The pentane sulphonic acid enhanced peak shape for dextromethorphan and chlorpheniramine. The assay of the active drug substances was validated for use in quality control applications. Validation studies demonstrated that the procedure was accurate, linear, precise, reproducible and rugged. The method conformed to both USP and EC validation guidelines.

Acetaminophen↗