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Journal of Neural Transmission. General... 1995Orphenadrine has been used as an antiparkinsonian, antispastic and analgesic drug for many years. Here we show that orphenadrine inhibits [3H]MK-801 binding to the...
Orphenadrine has been used as an antiparkinsonian, antispastic and analgesic drug for many years. Here we show that orphenadrine inhibits [3H]MK-801 binding to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA)-receptor in homogenates of postmortem human frontal cortex with a Ki-value of 6.0 +/- 0.7 microM. The NMDA receptor antagonistic effects of orphenadrine were assessed using concentration- and patch-clamp techniques on cultured superior colliculus neurones. Orphenadrine blocked open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner. The IC50-value against steady state currents at -70 mV was 16.2 +/- 1.6 microM (n = 6). Orphenadrine exhibited relatively fast, concentration-dependent open channel blocking kinetics (Kon 0.013 +/- 0.002 10(6) M-1S-1) whereas the offset rate was concentration-independent (Koff 0.230 +/- 0.004 S-1). Calculation of the ratio Koff/Kon revealed an apparent Kd-value of 17.2 microM which is nearly identical to the IC50 calculated at equilibrium.
Topics: Aged; Binding, Competitive; Cerebral Cortex; Dizocilpine Maleate; Electrophysiology; Excitatory Amino Acid Antagonists; Female; Humans; In Vitro Techniques; Ion Channel Gating; Male; Membranes; Middle Aged; Muscarinic Antagonists; Neurons; Orphenadrine; Patch-Clamp Techniques; Receptors, N-Methyl-D-Aspartate; Receptors, Phencyclidine; Superior Colliculi
PubMed: 8788072
DOI: 10.1007/BF01281158 -
Lancet (London, England) Jun 1985
Topics: Adult; Humans; Male; Orphenadrine; Seizures
PubMed: 2861328
DOI: 10.1016/s0140-6736(85)91803-3 -
Acta Pharmacologica Et Toxicologica Jul 1986Orphenadrine, a muscle relaxant with antinociceptive effects, was shown to increase and prolong the antinociceptive effects of paracetamol in mice. Both in the...
Orphenadrine, a muscle relaxant with antinociceptive effects, was shown to increase and prolong the antinociceptive effects of paracetamol in mice. Both in the increasing temperature hot plate test and in the formalin test, a combination of the two drugs showed a significantly improved effect compared to either of the drugs alone. The time course of the effects was tested in the increasing temperature hot plate test. The group treated with the drug combination showed a prolonged effect compared to both single drug treated groups, the effect lasting longer than 120 min. for the combination and about 80 min. for the single drugs. Orphenadrine and paracetamol increased antinociception even when orphenadrine was injected 90 min. after paracetamol, which by that time did not exert antinociceptive effects by itself. Thus the combination of orphenadrine and paracetamol enhances the antinociceptive effect of either drug in mice.
Topics: Acetaminophen; Animals; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Male; Mice; Orphenadrine; Pain; Time Factors
PubMed: 3766151
DOI: 10.1111/j.1600-0773.1986.tb00134.x -
Nederlands Tijdschrift Voor Geneeskunde Jul 1978
Topics: Adolescent; Adult; Arrhythmias, Cardiac; Blood Circulation; Central Nervous System; Female; Humans; Hypoventilation; Orphenadrine; Respiration; Suicide
PubMed: 673033
DOI: No ID Found -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2021The high prevalence of dorsalgia and dorsopathy among the adult population makes a significant contribution to the structure of the financial burden of health care...
The high prevalence of dorsalgia and dorsopathy among the adult population makes a significant contribution to the structure of the financial burden of health care systems. The use of non-steroidal anti-inflammatory drugs (NSAIDs) as the basis for the pharmacotherapy of dorsopathy is recommended by most international clinical guidelines. The pharmacodynamic effects of NSAIDs underlie the clinical efficacy of this group of drugs in patients with pain of musculoskeletal origin, while monotherapy is not always accompanied by the rapid development of a persistent analgesic effect. An urgent direction in the therapy of dorsopathies may include combination of NSAIDs with analgesic drugs of other pharmacological groups capable of additive action. The fixed combination of diclofenac, 75 mg, and orphenadrine, 50 mg, allows achieving an effective analgesic effect in patients with lower back pain of various etiologies. It was demonstrated in a series of clinical cases that included 4 patients with dorsopathy who were treated at the City Clinical Hospital No. 24, Moscow in 2020.
Topics: Adult; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Moscow; Orphenadrine
PubMed: 34184488
DOI: 10.17116/jnevro2021121051126 -
Archives of Toxicology. Supplement. =... 1980Eight cases of Orphenadrine intoxication were treated in the Resuscitation Centre of Rome's University Medical School. All these cases arrived in coma, after taking an...
Eight cases of Orphenadrine intoxication were treated in the Resuscitation Centre of Rome's University Medical School. All these cases arrived in coma, after taking an overdose of Orphenadrine in an attempt at suicide. The clinical signs and therapy are reported in detail; the cardiovascular side-effects, in particular those involving arrhythmias are dangerous and life threatening. From the clinical data it is believed that these changes in rhythm are mostly due to the autonomic nervous system (A.N.S.). In fact all the 8 patients survived, without treatment never having been treated with cardiokinetic or antiarrhythmic drugs, but a few were given Diazepam as well as respiratory assistance, cardiovascular assistance, and forced diuresis.
Topics: Adolescent; Adult; Female; Heart Diseases; Humans; Male; Orphenadrine; Suicide
PubMed: 6933954
DOI: 10.1007/978-3-642-67729-8_98 -
Clinical Oral Investigations May 2022The aim of this prospective, randomized, double-blind, controlled clinical study was to evaluate the analgesic effect of ibuprofen versus diclofenac plus orphenadrine on... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
The aim of this prospective, randomized, double-blind, controlled clinical study was to evaluate the analgesic effect of ibuprofen versus diclofenac plus orphenadrine on postoperative pain in orthognathic surgery.
MATERIAL AND METHODS
Patients who underwent orthognathic surgery were randomized into two groups to receive intravenously either 600 mg of ibuprofen (I-group) or 75 mg diclofenac plus 30 mg orphenadrine (D-group), both of which were given twice daily. Additionally, both groups were given metamizole 500 mg. Rescue pain medication consisted of acetaminophen 1000 mg and piritramide 7.5 mg as needed. To assess the pain intensity, the primary end point was the numeric rating scale (NRS) recorded over the course of the hospital stay three times daily for 3 days.
RESULTS
One hundred nine patients were enrolled (age range, 18 to 61 years) between May 2019 and November 2020. Forty-eight bilateral sagittal split osteotomies (BSSO) and 51 bimaxillary osteotomies (BIMAX) were performed. Surgical subgroup analysis found a significant higher mean NRS (2.73 vs.1.23) in the BIMAX D-group vs. I-group (p = 0.015) on the third postoperative day. Additionally, as the patient's body mass index (BMI) increased, the mean NRS (r = 0.517, p = 0.001) also increased. No differences were found between age, gender, length of hospital stay, weight, operating times, number of patients with complete pain relief, acetaminophen or piritramide intake, and NRS values. No adverse events were observed.
CONCLUSION
The results of this study demonstrate that ibuprofen administration and lower BMI were associated with less pain for patients who underwent bimaxillary osteotomy on the third postoperative day. Therefore, surgeons may prefer ibuprofen for more effective pain relief after orthognathic surgery.
CLINICAL RELEVANCE
Ibuprofen differs from diclofenac plus orphenadrine in class and is a powerful analgetic after orthognathic surgery.
Topics: Acetaminophen; Adolescent; Adult; Diclofenac; Double-Blind Method; Humans; Ibuprofen; Middle Aged; Orphenadrine; Orthognathic Surgery; Pain, Postoperative; Pirinitramide; Prospective Studies; Young Adult
PubMed: 35103836
DOI: 10.1007/s00784-022-04381-5 -
The Journal of Pharmacology and... Feb 1971
Topics: Acetates; Alcohols; Benzyl Compounds; Biopharmaceutics; Biotransformation; Chromatography, Thin Layer; Dealkylation; Ethers; Glucuronates; Glucuronidase; Humans; Male; Mass Spectrometry; Orphenadrine; Sulfates; Toluene; Tritium
PubMed: 5568779
DOI: No ID Found -
Emergency Medicine Australasia : EMA Aug 2022
Topics: Eating; Electrocardiography; Humans; Orphenadrine; Tachycardia, Sinus
PubMed: 35640918
DOI: 10.1111/1742-6723.14027 -
Drug Metabolism and Disposition: the... Mar 1997The specificities of orphenadrine and methimazole on eight human liver P450 enzyme activities were evaluated by studying the extent of inhibition at different...
The specificities of orphenadrine and methimazole on eight human liver P450 enzyme activities were evaluated by studying the extent of inhibition at different concentrations in two protocols: competitive inhibition and preincubation. In the competitive inhibition protocol, orphenadrine decreased CYP2B6 marker activity up to 45-57% in human liver microsomes and up to 80-97% in cell microsomes containing cDNA-expressed CYP2B6. Orphenadrine strongly decreased CYP2D6 marker activity by 80-90%. Orphenadrine also partially decreased the CYP1A2, CYP2A6, CYP3A4, and CYP2C19 marker activities. In the preincubation protocol, orphenadrine decreased the CYP2B6 activity in cDNA-expressed cell microsomes to completion. In human liver microsomes, orphenadrine strongly decreased the marker activities of CYP2B6, CYP2D6, as well as CYP2C9; and partially decreased the marker activities of CYP1A2, CYP2A6, CYP3A4, and CYP2C19. In the competitive inhibition protocol, methimazole had no effect on the marker activities of CYP2E1 and CYP2A6; slightly decreased CYP2D6 marker activity; partially decreased the marker activities of CYP2C19, CYP2C9, and CYP2B6; and dramatically decreased CYP3A4 marker activity. Methimazole decreased CYP1A2 marker activity at lower concentrations, but not at the highest concentration studied (1 mM). In the preincubation protocol, methimazole was shown to be a potent and nonspecific inhibitor of all the enzyme activities. Marker activities of CYP2C9, CYP2C19, and CYP3A4 were completely inhibited at relatively low concentrations. This study indicates orphenadrine cannot be used as a selective inhibitor of CYP2B6 in human liver microsomes and that methimazole is not a selective inhibitor of the flavin-containing monooxygenase in human liver microsomes.
Topics: Antiparkinson Agents; Antithyroid Agents; Binding, Competitive; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Humans; Isoenzymes; Methimazole; Microsomes, Liver; Orphenadrine; Sensitivity and Specificity
PubMed: 9172960
DOI: No ID Found