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[PMID]: 25476278 [Au] Autor: Abd El-Rahman MK; Zaazaa HE; Badr ElDin N; Moustafa AA [Ad] Endereço: Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr-El Aini Street, Cairo 11562, Egypt. [Ti] Título: Novel strategy for online monitoring of the degradation kinetics of propantheline bromide via a calixarene-based ion-selective electrode. [So] Source: Talanta;132:52-8, 2015 Jan. [Is] ISSN: 1873-3573 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Propantheline bromide (PB) is a hydrolysable anti-cholinergic drug. A novel strategy for the online monitoring of PB degradation kinetics catalysed by hydroxyl ions is presented. This is achieved by the incorporation of an on-site PB-selective electrode constructed using as an ionophore. This sensor was used to track the hydrolysis of PB by continuous measurement of the decrease in the produced emf over time. The use of this new technique provides real-time observation and yields a continuous profile of the hydrolysis behaviour of PB under various pH conditions as well as the temperature dependency of each reaction. Moreover, a great advantage of this proposed on-line system is its higher accuracy for rate constant estimation relative to other off-line methods. This kinetic data analysis permitted the determination of the hydrolysis activation energy and prediction of the drug shelf life. The estimated activation energy from Arrhenius plot was 20.77 kcal mol(-1). [Mh] Termos MeSH primário: Calixarenos/química Ionóforos/química Antagonistas Muscarínicos/análise Sistemas On-Line/instrumentação Potenciometria/instrumentação Propantelina/análise [Mh] Termos MeSH secundário: Tampões (Química) Estabilidade de Medicamentos Seres Humanos Concentração de Íons de Hidrogênio Hidrólise Eletrodos Íon-Seletivos Cinética Potenciometria/métodos Soluções Temperatura Ambiente Termodinâmica [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Buffers); 0 (Ionophores); 0 (Muscarinic Antagonists); 0 (Solutions); 130036-26-9 (Calixarenes); 1306V2B0Q8 (Propantheline) [Em] Mês de entrada: 1507 [Cu] Atualização por classe: 141205 [Lr] Data última revisão: 141205 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 141206 [St] Status: MEDLINE

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[PMID]: 24351551 [Au] Autor: Miyazaki M; Nishimura C; Minamida M; Iwanaga K; Kakemi M [Ad] Endereço: Department of Pharmaceutics, Osaka University of Pharmaceutical Sciences. [Ti] Título: Pharmacokinetic assessment of absorptive interaction of oral etoposide and morphine in rats. [So] Source: Biol Pharm Bull;37(3):371-7, 2014. [Is] ISSN: 1347-5215 [Cp] País de publicação: Japan [La] Idioma: eng [Ab] Resumo: Etoposide and morphine are well known P-glycoprotein (P-gp) substrates. The pharmacokinetic effect of morphine on plasma etoposide concentration after the oral concomitant use of etoposide and morphine in rats was assessed using a population analysis approach. A P-gp substrate quinidine and the anticholinergic drug propantheline were also administered with etoposide to compare with the effects of morphine. Plasma etoposide concentration after oral administration was well described using a linear 2-compartment open model with first-order kinetic absorption from the intestine, although a flip-flop phenomenon was shown. After administration of etoposide with morphine, an increased concentration and extended time at maximum concentration were observed compared with the administration of etoposide alone. However, coadministered quinidine significantly increased the maximum concentration without changing the time of the peak concentration of etoposide. Coadministered propantheline significantly extended the time at maximum concentration, although no changes in the peak concentration of etoposide were observed. These coadministered drugs resulted in different pharmacokinetic parameters of etoposide and acted as a significant covariate. That is, morphine and quinidine significantly increased the bioavailability of etoposide believed to be due to competitive P-gp inhibition in the intestine. In contrast, morphine and propantheline decreased the absorption rate constant and were associated with the suppression of enterokinesis. These results indicate that it is necessary to understand the effects on P-gp as well as have information on other effects on the gastrointestinal tract, such as enterokinesis suppression, and to appropriately assess the pharmacokinetic interactions of the combined oral use of P-gp substrate drugs. [Mh] Termos MeSH primário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo Interações Medicamentosas Etoposídeo/farmacocinética Morfina/farmacologia [Mh] Termos MeSH secundário: Administração Oral Animais Disponibilidade Biológica Etoposídeo/sangue Absorção Intestinal Masculino Propantelina/farmacologia Quinidina/farmacologia Ratos Ratos Wistar [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (ATP-Binding Cassette, Sub-Family B, Member 1); 1306V2B0Q8 (Propantheline); 6PLQ3CP4P3 (Etoposide); 76I7G6D29C (Morphine); ITX08688JL (Quinidine) [Em] Mês de entrada: 1410 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 131220 [St] Status: MEDLINE

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[PMID]: 23403246 [Au] Autor: Shaughnessy TK; Larson KJ; Polakowski JS; Martin RL [Ad] Endereço: AbbVie, North Chicago, IL, USA. thomas.shaughnessy@abbvie.com [Ti] Título: Pharmacological comparison of peristaltic effects in rats and mice. [So] Source: J Pharmacol Toxicol Methods;67(3):129-33, 2013 May-Jun. [Is] ISSN: 1873-488X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: INTRODUCTION: Conscious rodent models are commonly used to assess the effects of new chemical entities on propulsion (transit) time in the gastrointestinal system. This study was designed to compare three compounds clinically known to cause constipative (morphine sulfate and propantheline bromide) and laxative (metoclopramide hydrochloride) effects on transit time in rats and mice and to note if there are differences between the species. METHODS: Compounds were dosed in conscious rats and mice. At 0.5-2.0h post dosing (estimated time to maximal plasma concentration of each compound) animals were gavaged with an appropriate volume (based on weight) of 10% activated powdered carbon suspended in 5% gum arabic. Forty-five minutes following dosing the animals were sacrificed by CO2 asphyxiation and the small intestine was removed. The position of the leading edge of the charcoal was measured relative to the total length of the intestinal segment. RESULTS: The compounds tested produced variable statistical differences in transit time between species. Morphine and propantheline produced dose-dependent increases in transit time, and metoclopramide decreased transit time, statistically significant in both rodent models. DISCUSSION: The present data demonstrate that at similar doses rats and mice can be used interchangeably for transit studies. Mice were more sensitive to transit changes at higher doses of the compounds tested. [Mh] Termos MeSH primário: Motilidade Gastrointestinal/efeitos dos fármacos Trânsito Gastrointestinal/efeitos dos fármacos Intestino Delgado/efeitos dos fármacos Metoclopramida/farmacologia Morfina/farmacologia Peristaltismo/efeitos dos fármacos Propantelina/farmacologia [Mh] Termos MeSH secundário: Animais Intestino Delgado/fisiologia Masculino Camundongos Ratos Ratos Sprague-Dawley [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 1306V2B0Q8 (Propantheline); 76I7G6D29C (Morphine); L4YEB44I46 (Metoclopramide) [Em] Mês de entrada: 1403 [Cu] Atualização por classe: 130419 [Lr] Data última revisão: 130419 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 130214 [St] Status: MEDLINE

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[PMID]: 23228825 [Au] Autor: Baraldi C; Freguglia G; Tinti A; Sparta M; Alexandrova AN; Gamberini MC [Ad] Endereço: Department of Pharmaceutical Sciences, Institute of Pharmacy, University of Modena and Reggio Emilia, via Campi n. 183, 41100 Modena, Italy. [Ti] Título: IR, Raman and SERS spectra of propantheline bromide. [So] Source: Spectrochim Acta A Mol Biomol Spectrosc;103:1-10, 2013 Feb 15. [Is] ISSN: 1873-3557 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: The two known propantheline bromide polymorphs (form I and form II) were studied and characterized by a multianalytical approach. In the present work, the identification of propantheline bromide polymorphic forms through vibrational IR spectroscopies are presented and for the first time Raman microscopy and hot stage Raman microscopy (HSRM) studies are reported. Finally, quantum mechanical calculations were performed. For assisting the assignment of the experimental picks, the two IR spectra of the most and least stable representatives of a set of 56 conformers are calculated and studied. DSC thermograms data, are also reported. The surface enhanced Raman scattering (SERS) spectrum was also recorded in a silver colloid; it could be inferred that propantheline bromide is adsorbed on silver colloid through the oxygen atom with the molecular plane perpendicular to the metal surface. [Mh] Termos MeSH primário: Antiulcerosos/química Propantelina/química Espectroscopia de Infravermelho com Transformada de Fourier Análise Espectral Raman [Mh] Termos MeSH secundário: Cristalização Modelos Moleculares Análise Espectral Raman/métodos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Ulcer Agents); 1306V2B0Q8 (Propantheline) [Em] Mês de entrada: 1307 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 121212 [St] Status: MEDLINE

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[PMID]: 22983645 [Au] Autor: Ochi M; Inoue R; Yamauchi Y; Yamada S; Onoue S [Ad] Endereço: Department of Pharmacokinetics and Pharmacodynamics School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan. [Ti] Título: Development of meloxicam salts with improved dissolution and pharmacokinetic behaviors in rats with impaired gastric motility. [So] Source: Pharm Res;30(2):377-86, 2013 Feb. [Is] ISSN: 1573-904X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: PURPOSE: Because of its poor solubility in acidic solution, oral absorption and efficacy of meloxicam (MEL) may be reduced in severe pain patients with impaired gastric motility. The present study aimed to develop salt forms to overcome these drawbacks. METHOD: Upon MEL salt screening with eight counterions, five MEL salts were obtained. The physicochemical properties of these MEL salts were characterized with a focus on morphology, crystallinity, thermal behavior, dissolution, and chemical/photo-stability. Pharmacokinetic profiling of an orally administered MEL salt was also carried out in both normal rats and rats treated with propantheline for the suppression of gastric motility. RESULTS: Dissolution behaviors for all obtained MEL salts were markedly better than that of crystalline MEL; in particular, the initial dissolution rate of arginine MEL dihydrate (MEL/Arg) was ca. 14-fold higher than that of crystalline MEL. MEL/Arg was found to be chemically and physically stable. There was ca. 18-fold reduction of AUC(0-4) for orally dosed crystalline MEL (1.0 mg-MEL/kg) in propantheline-treated rats compared with that in normal rats. In contrast, there was only a ca. 3-fold difference in AUC(0-4) between normal and propantheline-treated rats after oral administration of MEL/Arg (1.0 mg-MEL/kg). CONCLUSION: From these findings, MEL/Arg may provide improved oral absorption in severe pain patients. [Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/administração & dosagem Anti-Inflamatórios não Esteroides/farmacocinética Motilidade Gastrointestinal Veículos Farmacêuticos/química Sais/química Tiazinas/administração & dosagem Tiazinas/farmacocinética Tiazóis/administração & dosagem Tiazóis/farmacocinética [Mh] Termos MeSH secundário: Administração Oral Animais Anti-Inflamatórios não Esteroides/sangue Área Sob a Curva Arginina/química Motilidade Gastrointestinal/efeitos dos fármacos Masculino Antagonistas Muscarínicos/farmacologia Propantelina/farmacologia Ratos Ratos Sprague-Dawley Solubilidade Tiazinas/sangue Tiazóis/sangue [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Muscarinic Antagonists); 0 (Pharmaceutical Vehicles); 0 (Salts); 0 (Thiazines); 0 (Thiazoles); 1306V2B0Q8 (Propantheline); 94ZLA3W45F (Arginine); VG2QF83CGL (meloxicam) [Em] Mês de entrada: 1307 [Cu] Atualização por classe: 171031 [Lr] Data última revisão: 171031 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 120918 [St] Status: MEDLINE [do] DOI: 10.1007/s11095-012-0878-2

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[PMID]: 22683390 [Au] Autor: Sundra TM; Harrison JL; Lester GD; Raidal SL; Phillips JK [Ad] Endereço: School of Veterinary and Biomedical Science, Faculty of Health Sciences, Murdoch University, Perth, 6150 WA, Australia. [Ti] Título: The influence of spasmolytic agents on heart rate variability and gastrointestinal motility in normal horses. [So] Source: Res Vet Sci;93(3):1426-33, 2012 Dec. [Is] ISSN: 1532-2661 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: The effects of hyoscine-N-butylbromide (hyoscine) and propantheline-bromide (propantheline) on heart rate (HR), HR variability (HRV) and gastrointestinal tract (GIT) contractions in the normal horse were determined. Five adult horses had ECG recordings for 180 min after treatment with propantheline (100mg), hyoscine (120 mg) or saline. Both propantheline and hyoscine reduced GIT sounds, with propantheline having a longer duration of effect (≥120 min). Both drugs elevated HR relative to the control baseline period (P<0.05), with the effects of propantheline again being of longer duration. HRV analysis indicated that propantheline suppressed Total Power (P<0.05), and both the high frequency (HF) and low frequency (LF) components of the power spectral analysis for up to 60-90 min post treatment. Hyoscine had no effect on HRV Total Power but reduced the HF component for 30 min after drug injection. Time domain variables correlated with Total Power and HF data (P<0.01). The marked effect of these compounds on parasympathetic control of cardiac and GIT function in normal horses should be taken into consideration when evaluating a clinical response to these agents. [Mh] Termos MeSH primário: Brometo de Butilescopolamônio/farmacologia Motilidade Gastrointestinal/efeitos dos fármacos Frequência Cardíaca/efeitos dos fármacos Cavalos/fisiologia Parassimpatolíticos/farmacologia Propantelina/farmacologia [Mh] Termos MeSH secundário: Animais Estudos Cross-Over [Pt] Tipo de publicação: JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Parasympatholytics); 1306V2B0Q8 (Propantheline); 2Z3E1OF81V (Butylscopolammonium Bromide) [Em] Mês de entrada: 1305 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 120612 [St] Status: MEDLINE

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[PMID]: 19881263 [Au] Autor: Nakade S; Ohno T; Ogawa M [Ti] Título: Response to "Suspected differential interactions of digoxin with imidafenacin and propantheline; some thoughts for introspection". [So] Source: Drug Metab Pharmacokinet;24(5):486-7, 2009. [Is] ISSN: 1880-0920 [Cp] País de publicação: England [La] Idioma: eng [Mh] Termos MeSH primário: Antagonistas Colinérgicos/farmacologia Digoxina/farmacologia Interações Medicamentosas/fisiologia Imidazóis/farmacologia Propantelina/farmacologia [Mh] Termos MeSH secundário: Disponibilidade Biológica Seres Humanos Quinuclidinas/farmacologia Receptores Muscarínicos/efeitos dos fármacos Succinato de Solifenacina Tetra-Hidroisoquinolinas/farmacologia [Pt] Tipo de publicação: COMMENT; LETTER [Nm] Nome de substância: 0 (Cholinergic Antagonists); 0 (Imidazoles); 0 (Quinuclidines); 0 (Receptors, Muscarinic); 0 (Tetrahydroisoquinolines); 1306V2B0Q8 (Propantheline); 73K4184T59 (Digoxin); KKA5DLD701 (Solifenacin Succinate); XJR8Y07LJO (imidafenacin) [Em] Mês de entrada: 1001 [Cu] Atualização por classe: 151119 [Lr] Data última revisão: 151119 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 091103 [St] Status: MEDLINE

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[PMID]: 19430177 [Au] Autor: Srinivas NR [Ti] Título: Suspected differential interactions of digoxin with imidafenacin and propantheline; some thoughts for introspection. [So] Source: Drug Metab Pharmacokinet;24(2):194-6, 2009. [Is] ISSN: 1880-0920 [Cp] País de publicação: England [La] Idioma: eng [Mh] Termos MeSH primário: Digoxina/farmacologia Imidazóis/farmacologia Propantelina/farmacologia [Mh] Termos MeSH secundário: Digoxina/efeitos adversos Digoxina/uso terapêutico Combinação de Medicamentos Interações Medicamentosas/fisiologia Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos Feminino Insuficiência Cardíaca/tratamento farmacológico Seres Humanos Imidazóis/efeitos adversos Masculino Propantelina/efeitos adversos [Pt] Tipo de publicação: COMMENT; LETTER [Nm] Nome de substância: 0 (Drug Combinations); 0 (Imidazoles); 1306V2B0Q8 (Propantheline); 73K4184T59 (Digoxin); XJR8Y07LJO (imidafenacin) [Em] Mês de entrada: 0911 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 090512 [St] Status: MEDLINE

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[PMID]: 18715548 [Au] Autor: Aghazadeh-Habashi A; Jamali F [Ad] Endereço: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta and EquiTech Corporation, Edmonton, Alta., Canada. [Ti] Título: Pharmacokinetics of meloxicam administered as regular and fast dissolving formulations to the rat: influence of gastrointestinal dysfunction on the relative bioavailability of two formulations. [So] Source: Eur J Pharm Biopharm;70(3):889-94, 2008 Nov. [Is] ISSN: 0939-6411 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: It is believed that acute pain suppresses nervus vagus, thereby, influencing gastrointestinal secretion and motility, which are the two factors that are necessary for disintegration and dissolution of solid dosage forms. We studied the pharmacokinetics of meloxicam and the effect of vagal suppression on the oral bioavailability and bioequivalence using a marketed (Brand) and a fast dissolving (FD) formulation. In simulated gastric juice, FD was disintegrated in 30s and released 30% of its meloxicam in 15 min and 60% in 2h. Brand was disintegrated in 4.5 min with a dissolution rate of 5.6% in 30 min that stayed plateau for the 2h experiment time. To suppress the vagus nerve, intraperitoneal injection of 20mg/kg propantheline 1 and 2h before meloxicam administration was used. Meloxicam (0.9 mg/kg) was administered to both control and vagally suppressed rats i.v. (n=4-6/group) as well as orally in a paired random fashion as broken pieces of Brand or FD tablets (n=7/ group). Serial (0-48h) blood samples were collected for pharmacokinetic and bioavailability studies. Relative bioavailability was measured according to a method in use for bioequivalence assessments. Systemic pharmacokinetics of meloxicam was not affected by vagal suppression. Absolute bioavailability of meloxicam, based on 0-48h measurement, was >0.68 regardless of the type of formulation and treatment. Vagal suppression, however, significantly reduced AUC(0-24) (microg h mL(-1)) for Brand (control, 58.8+/-22.0 vs treated, 22.1+/-9.7) but not for FD (control, 63.5+/-17.9 vs treated, 64.6+/-8.9) indicating a reduced absorption rate for the former. The peak time for Brand was also significantly delayed by over 20h for Brand and not for FD. Relative bioavailability was confirmed between FD and Brand that were in control but not in the vagally suppressed rats, indicating a disease-dependent bioequivalence. The effect of vagal suppression on the drug absorption rate can be obviated if the disintegration and dissolution become independent of gastrointestinal motility and secretion. [Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacocinética Motilidade Gastrointestinal Trato Gastrointestinal/inervação Absorção Intestinal Tiazinas/farmacocinética Tiazóis/farmacocinética Nervo Vago/fisiologia [Mh] Termos MeSH secundário: Administração Oral Animais Anti-Inflamatórios não Esteroides/administração & dosagem Anti-Inflamatórios não Esteroides/química Disponibilidade Biológica Química Farmacêutica Suco Gástrico/química Motilidade Gastrointestinal/efeitos dos fármacos Absorção Intestinal/efeitos dos fármacos Antagonistas Muscarínicos/farmacologia Projetos Piloto Propantelina/farmacologia Ratos Ratos Sprague-Dawley Solubilidade Comprimidos Tiazinas/administração & dosagem Tiazinas/química Tiazóis/administração & dosagem Tiazóis/química Nervo Vago/efeitos dos fármacos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Muscarinic Antagonists); 0 (Tablets); 0 (Thiazines); 0 (Thiazoles); 1306V2B0Q8 (Propantheline); VG2QF83CGL (meloxicam) [Em] Mês de entrada: 0901 [Cu] Atualização por classe: 161124 [Lr] Data última revisão: 161124 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 080822 [St] Status: MEDLINE [do] DOI: 10.1016/j.ejpb.2008.07.013

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[PMID]: 18495644 [Au] Autor: Syed Sheriff RJ; Au K; Cahill C; Duggan L; He Y; Udu V; Xia J [Ad] Endereço: Health Services and Population Research Department, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. rebecca.syed@iop.kcl.ac.uk [Ti] Título: Pharmacological interventions for clozapine-induced hypersalivation. [So] Source: Schizophr Bull;34(4):611-2, 2008 Jul. [Is] ISSN: 0586-7614 [Cp] País de publicação: United States [La] Idioma: eng [Mh] Termos MeSH primário: Antipsicóticos/efeitos adversos Clozapina/efeitos adversos Antagonistas dos Receptores Histamínicos/uso terapêutico Antagonistas Muscarínicos/uso terapêutico Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos Sialorreia/induzido quimicamente Sialorreia/tratamento farmacológico [Mh] Termos MeSH secundário: Antipsicóticos/uso terapêutico Astemizol/uso terapêutico China Clozapina/uso terapêutico Doxepina/uso terapêutico Seres Humanos Medicina Tradicional Chinesa Efeito Placebo Propantelina/uso terapêutico Ensaios Clínicos Controlados Aleatórios como Assunto/normas Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Antipsychotic Agents); 0 (Histamine Antagonists); 0 (Muscarinic Antagonists); 1306V2B0Q8 (Propantheline); 1668-19-5 (Doxepin); 7HU6337315 (Astemizole); J60AR2IKIC (Clozapine) [Em] Mês de entrada: 0809 [Cu] Atualização por classe: 140903 [Lr] Data última revisão: 140903 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 080523 [St] Status: MEDLINE [do] DOI: 10.1093/schbul/sbn043

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