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Saudi Pharmaceutical Journal : SPJ :... Oct 2010A validated method using capillary electrophoresis was developed, for the determination of orphenadrine citrate in its tablet formulations, in the presence of...
A validated method using capillary electrophoresis was developed, for the determination of orphenadrine citrate in its tablet formulations, in the presence of paracetamol. The method employs a running buffer of 30 mM pentane sulfonate sodium, dissolved in 20 mM MOPS buffer pH 7.7. Samples were injected using hydrodynamic sample injection mode (25 mbar, for 25 s), using positive polarity of 25 kV, at a constant temperature of 30 °C. Samples of orphenadrine citrate alone or in mixture solutions with paracetamol were exposed to various degradation conditions, and were electrophoresed using the recommended condition. The method was found to be specific, linear (r (2) = 0.994), precise, accurate, and robust, with an LOQ of 0.02 mg/mL. The proposed method was successfully applied for measurement of the percentage per label of orphenadrine citrate in commercially available tablets.
PubMed: 23960732
DOI: 10.1016/j.jsps.2010.07.007 -
Journal of Physiotherapy 2010Which interventions for non-specific neck pain are effective in reducing pain or disability? (Meta-Analysis)
Meta-Analysis Review
QUESTION
Which interventions for non-specific neck pain are effective in reducing pain or disability?
DESIGN
Systematic review with meta-analysis of randomised controlled trials.
PARTICIPANTS
Adults with non-specific neck pain.
INTERVENTION
All interventions for neck pain that were evaluated in trials with a placebo, minimal- or no-intervention control.
OUTCOME MEASURES
Pain and disability outcomes (0-100 scale) at the conclusion of a course of treatment (short term), and in the medium (3 to 9 months) and long (> 9 months) term.
RESULTS
33 trials were identified. The interventions with significant short-term effects on pain were manipulation (MD -22, 95% CI -32 to -11), multimodal intervention (MD -21, 95% CI -34 to -7), specific exercise (MD -12, 95% CI -22 to -2), combination orphenadrine/paracetamol (MD -17, 95% CI -32 to -2), and manual therapy (MD -12, 95% CI -16 to -7). There was a significant short-term effect on disability for acupuncture (MD -8, 95% CI -13 to -2) and manual therapy (MD -6, 95% CI -11 to -2). Treatment with laser therapy resulted in better pain outcomes at medium-term follow-up but not at short-term follow-up. No other intervention demonstrated medium- or long-term effects.
CONCLUSION
Some conservative interventions for neck pain are effective in the short term. Few interventions that have been investigated have shown longer term effects that are better than placebo or minimal intervention.
Topics: Acupuncture Therapy; Adult; Disability Evaluation; Electric Stimulation Therapy; Exercise Therapy; Humans; Laser Therapy; Magnetics; Neck Pain; Physical Therapy Modalities; Randomized Controlled Trials as Topic; Relaxation Therapy
PubMed: 20482474
DOI: 10.1016/s1836-9553(10)70037-0 -
Journal of Pharmacy & Pharmaceutical... 2010This study was performed to find which types of hepatic CYP isoforms are responsible for the metabolism of mirodenafil (a new erectogenic) and one of its metabolite,...
Pharmacokinetics of mirodenafil, a new erectogenic, and its metabolite, SK3541, in rats: involvement of CYP1A1/2, 2B1/2, 2D subfamily, and 3A1/2 for the metabolism of both mirodenafil and SK3541.
PURPOSE
This study was performed to find which types of hepatic CYP isoforms are responsible for the metabolism of mirodenafil (a new erectogenic) and one of its metabolite, SK3541, using various hepatic CYP inducers and inhibitors in rats.
METHODS
Mirodenafil at a dose of 20 mg/kg was administered intravenously to control rats and rats pretreated with various CYP inducers and inhibitors. The disappearance of SK3541 was also measured in vitro hepatic microsomes of rats with and without CYP inducer and inhibitors.
RESULTS
Compared to controls, in rats pretreated with 3-methylcholanthrene, orphenadrine, and dexamethasone (main inducers of CYP1A1/2, 2B1/2, and 3A1/2, respectively), the non-renal clearances (CLNRs) of mirodenafil were significantly faster (by 39.4%, 59.3%, and 63.9%, respectively). However, compared to controls, in rats pretreated with quinine and troleandomycin (main inhibitors of CYP2D subfamily and 3A1/2, respectively), the CLNRs of mirodenafil were significantly slower (by 36.1% and 33.2%, respectively). In rat hepatic microsomes spiked with furafylline, quinine, and troleandomycin (main inhibitors of CYP1A2, 2D subfamily, and 3A1/2, respectively), the intrinsic clearances (CLints) for the disappearance of SK3541 were significantly slower (by 18.4%, 35.3%, and 51.5%, respectively) than controls. Also in rat hepatic microsomes pretreated with orphenadrine (a main inducer of CYP2B1/2), the CLint for the disappearance of SK3541 was significantly faster (by 55.5%) than controls.
CONCLUSIONS
The above data suggest that hepatic CYP1A1/2, 2B1/2, 2D subfamily, and 3A1/2 are involved in the metabolism of both mirodenafil and SK3541 in rats.
Topics: Animals; Cytochrome P-450 Enzyme System; Enzyme Induction; Enzyme Inhibitors; Male; Microsomes, Liver; Phosphodiesterase 5 Inhibitors; Pyrimidinones; Rats; Rats, Sprague-Dawley; Sulfonamides
PubMed: 20456834
DOI: 10.18433/j3688m -
Acta Crystallographica. Section E,... Feb 2010The asymmetric unit of the title compound N,N-dimethyl-2-[(2-methyl-phen-yl)phenyl-meth-oxy]ethanaminium picrate picric acid, C(18)H(24)NO(+)·C(6)H(2)N(3)O(7)...
The asymmetric unit of the title compound N,N-dimethyl-2-[(2-methyl-phen-yl)phenyl-meth-oxy]ethanaminium picrate picric acid, C(18)H(24)NO(+)·C(6)H(2)N(3)O(7) (-)·C(6)H(3)N(3)O(7), contains one orphenadrinium cation, one picrate anion and one picric acid mol-ecule. In the orphenadrine cation, the two aromatic rings form a dihedral angle of 70.30 (7)°. There is an intra-molecular O-H⋯O hydrogen bond in the picric acid mol-ecule, which generates an S(6) ring motif. In the crystal structure, the orphenadrine cations, picrate anions and picric acid mol-ecules are connected by strong inter-molecular N-H⋯O hydrogen bonds, π⋯π inter-actions between the benzene rings of cations and anions [centroid-centroid distance = 3.5603 (9) Å] and weak C-H⋯O hydrogen bonds, forming a three-dimensional network.
PubMed: 21580426
DOI: 10.1107/S1600536810006379 -
Pharmacological Reports : PR 2009Orphenadrine is an anticholinergic drug used in the treatment of Parkinson's disease, and is also known to exert nonspecific antagonistic activity at the phencyclidine... (Comparative Study)
Comparative Study
Orphenadrine is an anticholinergic drug used in the treatment of Parkinson's disease, and is also known to exert nonspecific antagonistic activity at the phencyclidine binding site of the N-methyl-D-aspartate (NMDA) receptor. The aim of this study was to assess the anticonvulsant properties of orphenadrine and to evaluate its effect on the anticonvulsant activity of antiepileptic drugs against maximal electroshock-induced seizures in mice. Orphenadrine given at a dose of 5.65 mg/kg elevated the electrical seizure threshold from 5.7 (5.4-6.1) to 6.8 (6.3-7.3) mA, while a dose of 2.8 mg/kg was ineffective. The ED(50) values of orphenadrine administered 10, 30 and 120 min before maximal electroshock-induced convulsions were 16.8 (11.3-25.1), 17.8 (15.7-20.0) and 25.6 (23.3-28.3) mg/kg, respectively. Orphenadrine at a sub-threshold dose of 2.8 mg/kg significantly enhanced the anticonvulsant activity of valproate by reducing its ED(50) value from 315.8 (270.0-369.4) to 245.9 (207.1-292.0) mg/kg without affecting the free plasma levels of valproate. However, orphenadrine failed to enhance the protective activity of carbamazepine, phenytoin, phenobarbital, lamotrigine, topiramate, or oxcarbazepine against maximal electroshock-induced seizures.
Topics: Animals; Anticonvulsants; Drug Synergism; Electroshock; Male; Mice; Neuroprotective Agents; Orphenadrine; Random Allocation; Seizures
PubMed: 19815957
DOI: 10.1016/s1734-1140(09)70127-6 -
British Journal of Clinical Pharmacology Aug 2009Extrapyramidal side-effects induced by antipsychotic drugs are treated with dose reduction or substitution with another antipsychotic drug or by the addition of...
AIMS
Extrapyramidal side-effects induced by antipsychotic drugs are treated with dose reduction or substitution with another antipsychotic drug or by the addition of anticholinergic antiparkinson agents. The withdrawal of orphenadrine from the Norwegian market provided a possibility to investigate to what degree these alternative measures were taken in clinical practice.
METHODS
Data were drawn from the Norwegian Prescription Database on the sales of antipsychotics and one of the two anticholinergic antiparkinson agents marketed in 2004, orphenadrine and biperiden, to a total of 39 758 outpatients. The patients were reinvestigated in 2007. The consequences of the withdrawal of orphenadrine from the Norwegian market in 2005 regarding dosing, switching and cessation of antipsychotics and use of anticholinergics were assessed for orphenadrine users compared with biperiden users.
RESULTS
Of the patients originally using orphenadrine, 28.4% stopped using the drug without reducing the antipsychotic dose or replacing orphenadrine with another anticholinergic agent. The corresponding number for biperiden users was 19.3%. Only 11.8% of patients switched to another antipsychotic drug, but they used significantly lower antipsychotic doses than those who stayed on the same drug.
CONCLUSION
The use of anticholinergic antiparkinson agents could be seen as superfluous for at least one-third of patients.
Topics: Antipsychotic Agents; Cholinergic Antagonists; Drug Administration Schedule; Female; Humans; Male; Norway; Orphenadrine; Parkinson Disease; Practice Patterns, Physicians'; Safety-Based Drug Withdrawals; Substance Withdrawal Syndrome
PubMed: 19694744
DOI: 10.1111/j.1365-2125.2009.03446.x -
Journal of Neurochemistry Apr 2009Inactivation of testosterone by specific hydroxylations is a main function of cytochrome P450 (P450, CYP) in the brain. Recent data imply that induction of brain P450s... (Comparative Study)
Comparative Study
Inactivation of testosterone by specific hydroxylations is a main function of cytochrome P450 (P450, CYP) in the brain. Recent data imply that induction of brain P450s by neuroactive drugs alters steroid hormone levels and endocrine signalling, giving rise to endocrine disorders. In this study, we investigated this drug-hormone crosstalk in mouse brain. Phenytoin led to a significant increase of 2alpha-, 2beta-, 6beta-, 16alpha- and 16beta-hydroxytestosterones, while 6alpha- and 15alpha-hydroxytestosterones showed no significant alteration of their metabolism compared with untreated controls. Inhibition of testosterone hydroxylation using the chemical inhibitors orphenadrine, chloramphenicol, ketoconazole and nifedipine as well as antibodies against CYP3A- and 2B-isoforms pointed to major role of Cyp3a11 and an only minor function of Cyp2b9/10 in mouse brain. Cyp3a11 revealed to be the major isoform affected by phenytoin. There was considerable overlap of Cyp3a11 and AR expression in neuronal structures of the limbic system, namely the hippocampus, amygdala, hypothalamus and thalamus. Phenytoin treatment led to an increase of both, Cyp3a11 and AR expression in the limbic system. Additionally, the coherence between CYP3A and AR expression was analysed in PC-12 cells. Inhibition of phenytoin-induced endogenous CYP3A2 and AR by ketoconazole led a reduction of their expression to basal levels. We conclude that Cyp3a11 plays a crucial role in directing drug action to hormonal response within the limbic system of mouse brain in a so-called drug-hormone crosstalk.
Topics: Animals; Brain; Cytochrome P-450 CYP3A; Gene Expression Regulation, Enzymologic; Inactivation, Metabolic; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Oxidation-Reduction; PC12 Cells; Rats; Receptors, Androgen; Testosterone; Time Factors; Up-Regulation; Xenobiotics
PubMed: 19226368
DOI: 10.1111/j.1471-4159.2009.05994.x -
British Journal of Clinical Pharmacology Feb 2009Anticholinergic antiparkinson drugs are used to ameliorate extrapyramidal symptoms caused by either Parkinson's disease or antipsychotic drugs, but their use in the...
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
Anticholinergic antiparkinson drugs are used to ameliorate extrapyramidal symptoms caused by either Parkinson's disease or antipsychotic drugs, but their use in the treatment of Parkinson's disease is assumed to be in decline. Patients with psychotic conditions have a high prevalence of abuse of drugs, including anticholinergic antiparkinson drugs.
WHAT THIS STUDY ADDS
Anticholinergic antiparkinson drugs in Norway were primarily prescribed to patients using antipsychotic medication. The risk of abuse of this group of drugs was small, even among patients who probably abused other drugs.
AIMS
The use of anticholinergic antiparkinson drugs is assumed to have shifted from the therapy of Parkinson's disease to the amelioration of extrapyramidal adverse effects induced by antipsychotic drugs. There is a considerable body of data suggesting that anticholinergic antiparkinson drugs have a potential for abuse. The aim was to investigate the use and potential abuse of this class of drugs in Norway.
METHODS
Data were drawn from the Norwegian Prescription Database on sales to a total of 73 964 patients in 2004 of biperiden and orphenadrine, and use in patients with Parkinson's disease or in patients who were also prescribed antipsychotic agents. Possible abuse of these drugs was assessed by the level of use, skewedness of use, indications of drug-seeking behaviour and concomitant use of benzodiazepine tranquillizers, a group of prescription drugs with a recognized potential for abuse.
RESULTS
Anticholinergic antiparkinson drugs were prescribed to 4.5% of all outpatients who used antipsychotic drugs. This outnumbered sales to patients with Parkinson's disease by >20 to 1. We found indications of abuse of benzodiazepine tranquillizers among patients using antipsychotics, but there were no clear indications of abuse of anticholinergics, even among patients who were strongly suspected of abuse of benzodiazepines.
CONCLUSIONS
Anticholinergic antiparkinson drugs were used primarily by patients with psychotic illnesses. These patients have a very high prevalence of legal and illegal drug abuse, but the risk of abuse of anticholinergic antiparkinson drugs seemed small.
Topics: Adolescent; Adult; Aged; Antiparkinson Agents; Antipsychotic Agents; Biperiden; Cholinergic Antagonists; Drug Utilization; Female; Humans; Male; Middle Aged; Norway; Orphenadrine; Parkinson Disease; Practice Patterns, Physicians'; Prescription Drugs; Substance-Related Disorders; Young Adult
PubMed: 19094158
DOI: 10.1111/j.1365-2125.2008.03342.x -
PloS One Feb 2008Non-coding CUG repeat expansions interfere with the activity of human Muscleblind-like (MBNL) proteins contributing to myotonic dystrophy 1 (DM1). To understand this...
Non-coding CUG repeat expansions interfere with the activity of human Muscleblind-like (MBNL) proteins contributing to myotonic dystrophy 1 (DM1). To understand this toxic RNA gain-of-function mechanism we developed a Drosophila model expressing 60 pure and 480 interrupted CUG repeats in the context of a non-translatable RNA. These flies reproduced aspects of the DM1 pathology, most notably nuclear accumulation of CUG transcripts, muscle degeneration, splicing misregulation, and diminished Muscleblind function in vivo. Reduced Muscleblind activity was evident from the sensitivity of CUG-induced phenotypes to a decrease in muscleblind genetic dosage and rescue by MBNL1 expression, and further supported by the co-localization of Muscleblind and CUG repeat RNA in ribonuclear foci. Targeted expression of CUG repeats to the developing eye and brain mushroom bodies was toxic leading to rough eyes and semilethality, respectively. These phenotypes were utilized to identify genetic and chemical modifiers of the CUG-induced toxicity. 15 genetic modifiers of the rough eye phenotype were isolated. These genes identify putative cellular processes unknown to be altered by CUG repeat RNA, and they include mRNA export factor Aly, apoptosis inhibitor Thread, chromatin remodelling factor Nurf-38, and extracellular matrix structural component Viking. Ten chemical compounds suppressed the semilethal phenotype. These compounds significantly improved viability of CUG expressing flies and included non-steroidal anti-inflammatory agents (ketoprofen), muscarinic, cholinergic and histamine receptor inhibitors (orphenadrine), and drugs that can affect sodium and calcium metabolism such as clenbuterol and spironolactone. These findings provide new insights into the DM1 phenotype, and suggest novel candidates for DM1 treatments.
Topics: Animals; Brain; DNA Repeat Expansion; Disease Models, Animal; Drosophila; Drosophila Proteins; Eye; Gene Dosage; Myotonic Dystrophy; Nuclear Proteins; RNA-Binding Proteins; Trinucleotide Repeats
PubMed: 18270582
DOI: 10.1371/journal.pone.0001595 -
Yakugaku Zasshi : Journal of the... Oct 2007The estimation of paracetamol and orphenadrine citrate in a multicomponent pharmaceutical dosage form by spectrophotometric method has been reported. Because of highly...
Determination of paracetamol and orphenadrine citrate in pharmaceutical tablets by modeling of spectrophotometric data using partial least-squares and artificial neural networks.
The estimation of paracetamol and orphenadrine citrate in a multicomponent pharmaceutical dosage form by spectrophotometric method has been reported. Because of highly interference in the spectra and the presence of non-linearity caused by the analyte concentrations which deviate from Beer and Lambert's law, partial least-squares (PLS) and artificial neural networks (ANN) techniques were used for the calibration. A validation set of spiked samples was employed for testing the accuracy and precision of the methods. Reasonably good recoveries were obtained with PLS for paracetamol and the use of an ANN allowed the estimation of orphenadrine citrate, a minor component which could not be adequately modeled by PLS. Three production batches of a commercial sample were analysed, and there was statistically no significant difference (P<0.05) between the results with the proposed method and those obtain with the official comparative method.
Topics: Acetaminophen; Analgesics; Analgesics, Non-Narcotic; Chemistry, Pharmaceutical; Neural Networks, Computer; Neuromuscular Agents; Orphenadrine; Software; Spectrophotometry; Tablets
PubMed: 17917430
DOI: 10.1248/yakushi.127.1723