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2.
Zhonghua Nan Ke Xue ; 15(8): 717-20, 2009 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-19852273

RESUMO

OBJECTIVE: To investigate the efficacy and safety of the alpha1-receptor inhibitor terazosin combined with chlormezanone in the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: A total of 168 CPPS patients, aged 20 -50 (mean 32.9) years and with the disease course of 3 months to 7 years (mean 17 months), were equally randomized into a terazosin group (n = 58), a chlormezanone group (n = 38) and a terazosin + chlormezanone (T + C) group (n = 72), and treated accordingly for 4 weeks. All the patients were scored on NIH-CPSI (National Institute of Health-Chronic Prostatitis Symptom Index) after the treatment and the therapeutic effects were compared among the three groups. RESULTS: Of the total number of patients, 159 completed the treatment and were evaluated, including 55 of the terazosin group, 35 of the chlormezanone group and 69 of the T + C group. After the treatment, the NIH-CPSI scores of the three groups decreased from 24.05 +/- 3.02 to 16.15 +/- 3.25 (mean 7.90), from 23.43 +/- 3.58 to 17.51 +/- 3.08 (mean 5.92), and from 23.93 +/- 3.30 to 15.01 +/- 3.08 (mean 8.92), respectively, with statistically significant differences from pretreatment (P < 0.05) as well as between the combined therapy group and the other two (P < 0.05). The adverse events included postural hypotension (17.1% in the terazosin group and 15.4% in the T + C group), dysspermatism (3.4% in the terazosin group only), lassitude, fatigue and anorexia (18.5% in the chlormezanone group and 12.6% in the T + C group). Nine of the patients failed to accomplish the treatment because of adverse events, 3 (5.2%) in the terazosin group, 3 (7.9%) in the chlormezanone group and 3 (12.6%) in the T + C group. CONCLUSION: Both terazosin and chlormezanone can relieve the symptoms in CP/CPPS patients and improve their life quality, but their combined use may produce a better efficacy than either terazosin or chlormezanone used alone.


Assuntos
Clormezanona/uso terapêutico , Dor Pélvica/tratamento farmacológico , Prazosina/análogos & derivados , Prostatite/tratamento farmacológico , Adulto , Doença Crônica , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Prazosina/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
3.
Wien Klin Wochenschr ; 118(3-4): 95-9, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16703253

RESUMO

UNLABELLED: Following introduction of the compulsory use of seat belts in cars, whiplash injuries of the cervical spine have become common in everyday practice. Current treatment approaches lead to resolution of the symptoms within a short time in most cases but cannot prevent a small proportion of patients developing persistent health problems. The effects of adjuvant treatment with laser acupuncture on the acute symptoms and the results one year after the injury were studied in this prospective, randomized, placebo-controlled single-blind study. One group of patients (n = 23) were treated with laser acupuncture (5 mW HeNe laser on 22 acupuncture points for 15 s each) plus cervical collar and a combination of paracetamol and chlormezanone; a second group (n = 22) received the same treatments but with the use of a placebo laser. The treatment was given three times per week until the patient was asymptomatic. No statistically significant advantage of the laser acupuncture treatment was found in the acute phase (mobility in all three planes, duration of pain and duration of use of a cervical collar) or the chronic phase (drug use and the incidences of chronic recurrent problems such as myofascial pain, headaches, vertigo and tinnitus). CONCLUSION: Adjuvant laser acupuncture with a 5 mW HeNe laser and an irradiation time of 15 s appears to be ineffective in the management of whiplash injuries.


Assuntos
Terapia por Acupuntura/métodos , Terapia com Luz de Baixa Intensidade , Traumatismos em Chicotada/terapia , Acetaminofen/administração & dosagem , Acetaminofen/uso terapêutico , Pontos de Acupuntura , Adolescente , Adulto , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/uso terapêutico , Clormezanona/administração & dosagem , Clormezanona/uso terapêutico , Interpretação Estatística de Dados , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Terapia a Laser , Masculino , Pessoa de Meia-Idade , Relaxantes Musculares Centrais/administração & dosagem , Relaxantes Musculares Centrais/uso terapêutico , Placebos , Estudos Prospectivos , Radioterapia Adjuvante , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Traumatismos em Chicotada/tratamento farmacológico , Traumatismos em Chicotada/radioterapia
4.
Skin Pharmacol Physiol ; 18(3): 132-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15897685

RESUMO

Chlormezanone is a centrally acting muscle relaxant introduced in human therapy as a racemic substance. The following investigation was performed in order to investigate whether the racemate and both enantiomers differ in their potential cytotoxicty in vitro. We investigated antiproliferative effects and cytotoxicity (PicoGreen and ATP assay) for human HaCaT keratinocytes, production of oxygen radicals (ROS) by human interleukin-3-stimulated leukocytes (Lucigenin assay) and production of sulfoleukotrienes (Cellular Antigen Stimulation Test - CAST) by human leukocytes. In the dosage range of 0.001 to 0.1 mg/ ml chlormezanone, no antiproliferative effects were measured with the racemate and both enantiomers. At 1.0 mg/ml, a decrease of proliferative activity was seen after 48 h incubation time of about 50% for the enantiomers and of about 80% for the racemate (PicoGreen) and 50% (enantiomers) or 21% (racemate) in the ATP assay, respectively. ROS production was significantly inhibited at concentrations < or =0.01 mg/ ml by the racemate and the (+)-enantiomer, whereas the (-)-enantiomer was less effective. There was no stimulation of sulfidoleukotrienes in human leukocytes by chlormezanone. Present data argue for absence of significant cytotoxicity against human HaCaT keratinocytes and a dose-dependent suppression of ROS production by human leukocytes that is not uniform among the racemate and its enantiomers.


Assuntos
Clormezanona/farmacologia , Queratinócitos/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Relaxantes Musculares Centrais/farmacologia , Trifosfato de Adenosina/metabolismo , Alérgenos , Células Cultivadas , Clormezanona/química , Corantes Fluorescentes , Humanos , Interleucina-3/farmacologia , Queratinócitos/metabolismo , Linfócitos/metabolismo , Relaxantes Musculares Centrais/química , Compostos Orgânicos , Espécies Reativas de Oxigênio/metabolismo , Estereoisomerismo
5.
Pharmazie ; 58(2): 95-8, 2003 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-12641322

RESUMO

2-(4-Chlorophenyl)-4-metathiazanone (2) is the intermediate product for the two step-synthesis of chlormezanone (1), a centrally acting muscle relaxant. The second step includes the oxidation of its sulfur atom. It has been found that the foregoing reaction of 4-chlorobenzaldehyde with methylamine forming the hemiaminale and the subsequent addition of beta-mercaptopropionic acid leads to a remarkable better yield (67% of th.) than the route via the hemimercaptale (42% of th.). 2 could be oxidized with sodium perborate superior to potassium permanganate. The racemic chlormezanone (1) is resolved quickly on a gram scale by preparative column chromatography on a Chiralcel OD column (tris(3,5-dimethyl-phenyl-carbamoyl)cellulose on silicagel). The resolution needed only 40 min, if flow rate, composition of the mobile phase and temperature as the most important factors are determined prior with an analytical column. Both dissociation constants could be determined for the first time with the aid of a log pKa-Titrator of the Sirius Co., which needs for the registration of the curves only 15-17 min in the pH range of 2-12. This speed outplayed the disturbing cleavage of the S-C bond of chlormezanone at strong acidic and alkaline pH values.


Assuntos
Clormezanona/síntese química , Relaxantes Musculares Centrais/síntese química , Clormezanona/química , Cromatografia por Troca Iônica , Concentração de Íons de Hidrogênio , Indicadores e Reagentes , Relaxantes Musculares Centrais/química , Oxirredução , Temperatura
10.
Pharmazie ; 55(4): 293-6, 2000 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-10798243

RESUMO

The enantinomers of chlormezanone (1) may be achieved by enantioselective HPLC separation with a yield of 98% using a OD-Daicel column. Both enantiomers bind to human serum albumin (HSA) at pH 7.4 to a range of 11-12%. Binding to the globuline fractions is much less (2-4%, equilibrium dialysis, validation by ultrafiltration). It could be demonstrated by means of 1H-NMR spectroscopy that 1 binds to HSA with the benzene ring as well as with the thiazanone ring. The velocity of racemization could be measured for the first time using a BSA column. The enantiomers undergo racemization at pH 7.4 and 37 degrees C with a halflife of approx. 20.5 h.


Assuntos
Clormezanona/química , Clormezanona/farmacologia , Relaxantes Musculares Centrais/química , Relaxantes Musculares Centrais/farmacologia , Cromatografia Líquida de Alta Pressão , Diálise , Humanos , Espectroscopia de Ressonância Magnética , Ligação Proteica , Albumina Sérica/metabolismo , Estereoisomerismo , Ultrafiltração
11.
Artigo em Inglês | MEDLINE | ID: mdl-10412893

RESUMO

Both chlormezanone enantiomers, for the first time obtained by enantiospecific HPLC with a 100% yield, bind to oxidized cytochrome P-450 in rat liver microsomes with a binding curve according to type I, similar to hexobarbital but less pronounced. There are no differences between the binding curves of the two enantiomers. Ethylmorphine N-demethylation, ethoxycoumarin and ethoxyresorufin O-deethylation are inhibited by both chlormezanone enantiomers at 0.1-1 mM concentrations: no differences could be found. Luminol and lucigenin amplified chemiluminescence indicating the formation of reactive oxygen species was not influenced by either enantiomer in concentration ranges between millimolar and micromolar, whereas hydrogen peroxide formation was inhibited. NADPH/Fe stimulated lipid peroxidation was not influenced. Scavenger activity could not be demonstrated: the zymosan stimulated whole blood chemiluminescence was not influenced significantly.


Assuntos
Clormezanona/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Microssomos Hepáticos/metabolismo , Relaxantes Musculares Centrais/metabolismo , Acridinas/química , Analgésicos Opioides/metabolismo , Animais , Anticoagulantes/metabolismo , Cromatografia Líquida de Alta Pressão , Cumarínicos/metabolismo , Etilmorfina/metabolismo , Peróxido de Hidrogênio/metabolismo , Indicadores e Reagentes/química , Peroxidação de Lipídeos/efeitos dos fármacos , Medições Luminescentes , Luminol/química , Masculino , Oxazinas/metabolismo , Ligação Proteica , Ratos , Espécies Reativas de Oxigênio/metabolismo , Estereoisomerismo , Zimosan/química
14.
Pharmazie ; 53(9): 620-4, 1998 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-9770210

RESUMO

Chlormezanone, a chiral centrally acting muscle relaxant, will be cleaved at its S-C-1 bond by an autoprotolytic process. The optimum of chemical stability exists between pH 2 up to pH 9 with a maximum at pH 7.4. The plasma half life at 37 degrees C is 76 h. Enzymes do attack the products of cleavage namely 4-chlorobenzaldehyde and 2-carboxyethane-sulfinic-acid-N-methyl-amide. The main metabolite in urine is 4-chlorohippuric acid in the range of up to 70% of the oral administered dose to humans. No cytochrome P-450 is engaged in the cleavage of the S-C-bond.


Assuntos
Clormezanona/farmacocinética , Relaxantes Musculares Centrais/farmacocinética , Biotransformação , Cromatografia Líquida de Alta Pressão , Meia-Vida , Humanos
15.
Dtsch Med Wochenschr ; 123(28-29): 866-70, 1998 Jul 10.
Artigo em Alemão | MEDLINE | ID: mdl-9693657

RESUMO

HISTORY AND CLINICAL FINDINGS: A 34-year-old woman was admitted for treatment of toxic epidermolysis of the skin and mucosa. 16 days previously she had started to take chlormezanone (Muskel Trancopal) and some other medications for pain in the shoulder and neck. On admission she had a fever of 39 degrees C and, in addition to the epidermolysis, diffuse abdominal pain on pressure and blood-streaked stool. INVESTIGATIONS: Liver enzyme activities (GOT 979 U/I, GPT 1496 U/I, gamma GT 201 U/I) alkaline phosphatase 515 U/I), bilirubin (3.9 mg/dl) and pancreatic enzyme activities were raised. Sonography was nondiagnostic, computed tomography demonstrated only a small amount of ascites. TREATMENT AND COURSE: The epidermolytic lesions, cholestatic hepatitis and pancreatitis markedly regressed under aseptic wound treatment, antibiotics and parenteral nutrition. Persistent blood-streaked stools and bilateral pneumonia with progressive respiratory failure developed. Despite intensive medical care the patient died after 14 days from protracted sepsis with multi-organ failure. Autopsy additionally revealed adult respiratory distress syndrome and complete loss of colonic mucosa. CONCLUSION: The severe course of a toxic epidermal necrosis with fatal outcome is the first such case reported in Germany that very probably was caused by chlormezanone. 4 weeks after this case was reported to the German Doctors' Drug Commission, the manufacturers of the drug withdrew it from the market.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Clormezanona/efeitos adversos , Relaxantes Musculares Centrais/efeitos adversos , Pancreatite/induzido quimicamente , Síndrome de Stevens-Johnson/etiologia , Doença Aguda , Adulto , Clormezanona/uso terapêutico , Colo/efeitos dos fármacos , Colo/patologia , Evolução Fatal , Feminino , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Relaxantes Musculares Centrais/uso terapêutico , Cervicalgia/tratamento farmacológico , Dor/tratamento farmacológico , Síndrome do Desconforto Respiratório/induzido quimicamente , Ombro
17.
Eur J Drug Metab Pharmacokinet ; 22(2): 165-71, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9248786

RESUMO

Chlormezanone binds to oxidized cytochrome P450 in rat liver microsomes with a binding curve according to type I like hexobarbital but less pronounced and with a general shift to the left. Ethylmorphine N-demethylation, ethoxycoumarin and ethoxyresorufin O-deethylation are inhibited by chlormezanone in mM concentrations only whereas pentoxyresorufin O-depentylation is inhibited by about 50% in microM concentrations. Luminol and lucigenin amplified chemiluminescence indicating the formation of reactive oxygen species was not influenced in concentration ranges between mM and microM, whereas NADPH/Fe stimulated lipid peroxidation showed a tendency of inhibition. But scavenger activity could not be demonstrated: the zymosan stimulated chemiluminescence of whole blood was not influenced significantly. The degradation process of chlormezanone was elucidated. The first step involves ring opening by chemical hydrolysis with subsequent formation of an unstable acylhalfaminal which is the source of 4-chlorobenzaldehyde. This aldehyde undergoes enzymatically controlled oxidation to 4-chlorobenzoic acid which is the parent compound of following phase II reactions. The second degradation product is 2-carboxyethane-sulfinic-acid-N-methylamide, which is hydrolyzed very quickly. Neither oxidation of the sulfinic acid or its N-methylamide derivative could be observed nor N-demethylation of chlormezanone.


Assuntos
Clormezanona/metabolismo , Clormezanona/farmacologia , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Relaxantes Musculares Centrais/metabolismo , Relaxantes Musculares Centrais/farmacologia , Animais , Biotransformação , Cumarínicos/metabolismo , Inibidores das Enzimas do Citocromo P-450 , Sistema Enzimático do Citocromo P-450/metabolismo , Interações Medicamentosas , Etilmorfina/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Medições Luminescentes , Masculino , Microssomos Hepáticos/enzimologia , Oxazinas/metabolismo , Oxigenases/antagonistas & inibidores , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Estimulação Química , Zimosan/farmacologia
18.
Int J Clin Pharmacol Ther ; 35(3): 112-6, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9089000

RESUMO

Eighteen male volunteers have been treated with 3 different oral formulations of chlormezanone according to a randomized 3-way change-over design. The test preparation was a tablet (Krewel), reference preparation 1 was a suspension (Krewel), and reference preparation 2 was a tablet (Muskel Trancopal, Sanofi Winthrop GmbH). All preparations contained 200 mg of chlormezanone. Divided in 3 periods the volunteers received single doses of the test and the 2 reference formulations, respectively. Blood samples have been drawn immediately prior to each administration and at 21 sampling points within 144 h after dosing. A wash-out period of 2 weeks was maintained between successive drug doses. Plasma concentrations of chlormezanone were determined by a validated reversed-phase HPLC method with UV detection, with a lower limit of quantification of 0.1 microgram/ml. The following mean values have been obtained for the test preparation: AUC0-infinity 121 micrograms x h/ml, Cmax of 2.9 micrograms/ml at 1.5 h, t1/2 38 h, after administration of the suspension: AUC0-infinity 111 micrograms x h/ml, Cmax 2.6 micrograms/ml, tmax 1.5 h, t1/2 40 h, and after administration of the reference tablet: AUC0-infinity 121 micrograms x h/ml, Cmax 3.0 micrograms/ml, tmax 1.6 h, t1/2 38 h. The test preparation shows a relative bioavailability of 109% compared to the suspension and has been proven to be bioequivalent to the reference tablet with regard to extent and rate of absorption.


Assuntos
Clormezanona/farmacocinética , Relaxantes Musculares Centrais/farmacocinética , Administração Oral , Adolescente , Adulto , Análise de Variância , Disponibilidade Biológica , Clormezanona/administração & dosagem , Clormezanona/sangue , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Humanos , Masculino , Relaxantes Musculares Centrais/administração & dosagem , Relaxantes Musculares Centrais/sangue , Padrões de Referência , Análise de Regressão , Espectrofotometria Ultravioleta , Equivalência Terapêutica
19.
Fortschr Med ; 114(35-36): 500-4, 1996 Dec 20.
Artigo em Alemão | MEDLINE | ID: mdl-9119352

RESUMO

METHOD: The analgesic and muscle-relaxing properties of flupirtine maleate, chlormezanone and placebo were compared in a total of 184 patients. Of these patients, 164 met the criteria of the treatment plan (intention to treat), and the data of 140 patients were finally evaluated in accordance with the test protocol. A positive response was defined as a reduction in pain intensity and muscle tension by 2 categories on the 5-category verbal scale "very severe/severe/moderate/mild/ none" on the seventh day of treatment. RESULTS: In the per-protocol-analysis the responder rate was 60.9% for flupirtine, 47.8% for chlormezanone, and 43.8% for placebo, the difference between drugs and placebo not being significant. The overall assessment of the physicians involved was very good/ good in 47.8% and satisfactory in 37.0% of the flupirtine group, very good/good in 45.6% and satisfactory in 17.4% of the chlormezanone group, the corresponding figures for the placebo group being 33.4% and 20.6%, respectively. Flupirtine was thus superior to placebo (p = 0.007). The incidence of adverse drug reactions was 14.8% (8/54) for flupirtine, 19.3% (11/57) for chlormezanone, and 7.3% (4/55) for placebo.


Assuntos
Aminopiridinas/administração & dosagem , Analgésicos/administração & dosagem , Clormezanona/administração & dosagem , Dor Lombar/tratamento farmacológico , Relaxantes Musculares Centrais/administração & dosagem , Síndromes da Dor Miofascial/tratamento farmacológico , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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