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1.
Pediatrics ; 146(Suppl 1): S93-S98, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32737240

RESUMO

A central tension in pediatric research ethics arises from our desire to protect children from harm while also allowing progress toward discoveries that could improve child health. A prime example of this tension is research on a controversial yet increasingly common practice: the use of cannabis by women to treat nausea and vomiting of pregnancy. Studies of cannabis use in pregnancy face a combination of ethical hurdles because of the inclusion of pregnant women and involvement of a schedule I controlled substance. Given the growing need for research on the safety and efficacy of cannabis for nausea and vomiting of pregnancy, we reflect on the multiple historical contexts that have contributed to the challenge of studying cannabis use during pregnancy and make a case for the ethical rationale for such research.


Assuntos
Ética em Pesquisa , Maconha Medicinal/uso terapêutico , Êmese Gravídica/terapia , Pediatria/ética , Gestantes , Sujeitos da Pesquisa , Antieméticos/efeitos adversos , Diciclomina/uso terapêutico , Doxilamina/uso terapêutico , Aprovação de Drogas , Combinação de Medicamentos , Feminino , Humanos , Maconha Medicinal/efeitos adversos , Ondansetron/uso terapêutico , Gravidez , Piridoxina/uso terapêutico , Teratógenos , Talidomida/efeitos adversos
3.
Sci Rep ; 9(1): 13990, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570736

RESUMO

Memory loss is one of the most tragic symptoms of Alzheimer's disease. Our laboratory has recently demonstrated that 'i-Extract' of Ashwagandha (Withania somnifera) restores memory loss in scopolamine (SC)-induced mice. The prime target of i-Extract is obscure. We hypothesize that i-Extract may primarily target muscarinic subtype acetylcholine receptors that regulate memory processes. The present study elucidates key target(s) of i-Extract via cellular, biochemical, and molecular techniques in a relevant amnesia mouse model and primary hippocampal neuronal cultures. Wild type Swiss albino mice were fed i-Extract, and hippocampal cells from naïve mice were treated with i-Extract, followed by muscarinic antagonist (dicyclomine) and agonist (pilocarpine) treatments. We measured dendritic formation and growth by immunocytochemistry, kallikrein 8 (KLK8) mRNA by reverse transcription polymerase chain reaction (RT-PCR), and levels of KLK8 and microtubule-associated protein 2, c isoform (MAP2c) proteins by western blotting. We performed muscarinic receptor radioligand binding. i-Extract stimulated an increase in dendrite growth markers, KLK8 and MAP2. Scopolamine-mediated reduction was significantly reversed by i-Extract in mouse cerebral cortex and hippocampus. Our study identified muscarinic receptor as a key target of i-Extract, providing mechanistic evidence for its clinical application in neurodegenerative cognitive disorders.


Assuntos
Memória/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Receptor Muscarínico M1/efeitos dos fármacos , Withania/química , Animais , Western Blotting , Dendritos/efeitos dos fármacos , Dendritos/fisiologia , Diciclomina/farmacologia , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Pilocarpina/farmacologia , Receptor Muscarínico M1/agonistas , Receptor Muscarínico M1/antagonistas & inibidores , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Escopolamina/farmacologia
4.
Nat Rev Dis Primers ; 5(1): 62, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515515

RESUMO

Nausea and vomiting of pregnancy (NVP) is a common condition that affects as many as 70% of pregnant women. Although no consensus definition is available for hyperemesis gravidarum (HG), it is typically viewed as the severe form of NVP and has been reported to occur in 0.3-10.8% of pregnant women. HG can be associated with poor maternal, fetal and child outcomes. The majority of women with NVP can be managed with dietary and lifestyle changes, but more than one-third of patients experience clinically relevant symptoms that may require fluid and vitamin supplementation and/or antiemetic therapy such as, for example, combined doxylamine/pyridoxine, which is not teratogenic and may be effective in treating NVP. Ondansetron is commonly used to treat HG, but studies are urgently needed to determine whether it is safer and more effective than using first-line antiemetics. Thiamine (vitamin B1) should be introduced following protocols to prevent refeeding syndrome and Wernicke encephalopathy. Recent advances in the genetic study of NVP and HG suggest a placental component to the aetiology by implicating common variants in genes encoding placental proteins (namely GDF15 and IGFBP7) and hormone receptors (namely GFRAL and PGR). New studies on aetiology, diagnosis, management and treatment are under way. In the next decade, progress in these areas may improve maternal quality of life and limit the adverse outcomes associated with HG.


Assuntos
Hiperêmese Gravídica/diagnóstico , Antieméticos/uso terapêutico , Diciclomina/uso terapêutico , Doxilamina/uso terapêutico , Combinação de Medicamentos , Feminino , Fator 15 de Diferenciação de Crescimento/análise , Humanos , Hiperêmese Gravídica/epidemiologia , Programas de Rastreamento/métodos , Náusea/etiologia , Gravidez , Piridoxina/uso terapêutico
5.
J Clin Epidemiol ; 116: 39-48, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31352006

RESUMO

OBJECTIVES: The aim of the study was to quantify the risk of major congenital malformations (MCM) associated with first-trimester exposure to antiemetics. STUDY DESIGN AND SETTING: Using the Quebec Pregnancy Cohort (1998-2015), first-trimester doxylamine-pyridoxine, metoclopramide, and ondansetron exposures were assessed for their association with MCM. Generalized estimating equations were used to estimate odds ratios (OR), adjusting for potential confounders (aOR). RESULTS: Within 17 years of follow-up, the prevalence of antiemetic use during pregnancy increased by 76%. Within our cohort, 45,623 pregnancies were exposed to doxylamine-pyridoxine, 958 to metoclopramide, and 31 to ondansetron. Doxylamine-pyridoxine and metoclopramide use were associated with an increased risk of overall MCM (aOR 1.07, 95% confidence interval [CI]: 1.03-1.11; 3,945 exposed cases) and (aOR 1.27, 95% CI: 1.03-1.57; 105 exposed cases), respectively. Doxylamine-pyridoxine exposure was associated with increased risks of spina bifida (aOR 1.87, 95% CI: 1.11-3.14; 23 exposed cases), nervous system (aOR 1.25, 95% CI: 1.06-1.47; 225 exposed cases), and musculoskeletal system defects (aOR 1.08, 95% CI: 1.02-1.14; 1,735 exposed cases). Metoclopramide exposure was associated with an increased risk of genital organ defects (aOR 2.26, 95% CI: 1.14-4.48; 10 exposed cases). No statistically significant association was found between ondansetron exposure and the risk of overall MCM. CONCLUSION: First-trimester doxylamine-pyridoxine and metoclopramide exposure was associated with a significantly increased risk of overall and specific MCM.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Antieméticos/efeitos adversos , Náusea/tratamento farmacológico , Vômito/tratamento farmacológico , Adulto , Antieméticos/uso terapêutico , Estudos de Coortes , Diciclomina/efeitos adversos , Diciclomina/uso terapêutico , Doxilamina/efeitos adversos , Doxilamina/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Masculino , Idade Materna , Metoclopramida/efeitos adversos , Metoclopramida/uso terapêutico , Ondansetron/efeitos adversos , Ondansetron/uso terapêutico , Gravidez , Primeiro Trimestre da Gravidez , Prevalência , Piridoxina/efeitos adversos , Piridoxina/uso terapêutico , Quebeque/epidemiologia , Adulto Jovem
8.
Eur J Pharm Sci ; 123: 387-394, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30077710

RESUMO

Spray-dried chitosan microparticles have been widely exploited as vehicles for mucosal drug delivery. Despite their advantages as pharmaceutical formulations, one of the major challenges is achieving sustained drug release, which would diminish toxicity and dosage frequency. The aim of this study was to formulate mucoadhesive glutaraldehyde cross-linked chitosan microparticles loaded with doxylamine succinate and pyridoxine hydrochloride as potential nasal drug delivery systems with sustained release. Microparticle models were formulated via spray-drying technique, using glutaraldehyde in different concentrations (0.1-1.0 mg/mL) as a cross-linking agent for chitosan. The obtained particles were with spherical shape, smooth surface and median diameter of 4 µm. The drug entrapment efficiency was high (80.47%-94.25%), indicating a tendency to decrease at higher glutaraldehyde concentrations. FTIR data demonstrated that there were no chemical interactions between glutaraldehyde and the drugs. The in vitro studies showed that the cross-linking process substantially limited particles swelling. The cross-linked particles exhibited sustained drug release characteristics at pH 6.8 over a period of 5 h with an initial burst-effect in the first 30 min. Drug release followed Korsmeyer-Peppas kinetics. Although a decrease of the particles mucoadhesive properties was observed after modification, all cross-linked formulations demonstrated high in vitro adsorption of mucin. The proposed models of mucoadhesive microsphere with sustained drug release are a perspective ground for further development of a novel delivery system for nasal administration of doxylamine and pyridoxine.


Assuntos
Antieméticos/química , Química Farmacêutica/métodos , Quitosana/química , Reagentes para Ligações Cruzadas/química , Diciclomina/química , Doxilamina/química , Portadores de Fármacos , Glutaral/química , Piridoxina/química , Adesividade , Administração Intranasal , Antieméticos/administração & dosagem , Preparações de Ação Retardada , Diciclomina/administração & dosagem , Doxilamina/administração & dosagem , Combinação de Medicamentos , Composição de Medicamentos , Liberação Controlada de Fármacos , Estudos de Viabilidade , Mucinas Gástricas/química , Cinética , Microesferas , Piridoxina/administração & dosagem , Solubilidade
9.
J Antibiot (Tokyo) ; 71(4): 456-466, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29348527

RESUMO

Dicyclomine is a human muscarinic acetylcholine receptor antagonist used for the treatment of abdominal cramps. We are reporting here that dicyclomine can inhibit the in vitro growth and virulence factors of the human pathogen Candida albicans very effectively. Dicyclomine inhibited adhesion, early biofilm, mature biofilm, and planktonic growth. Yeast to hyphal form transition of C. albicans in various inducer media such as serum, proline, glucose, and N-acetylglucosamine was inhibited. Dicyclomine also could kill C. albicans cells within 15 min of exposure. Dicyclomine appears to inhibit the yeast to hyphal conversion by affecting signal transduction pathway. The expression of selected genes associated with yeast to hyphal form transition in serum in presence of dicyclomine was studied using real-time polymerase chain reaction (RtPCR). The RtPCR analysis showed that dicyclomine targets both cAMP pathway as well as MAPK cascade. Eight genes were upregulated. Out of these, three major upregulated genes were Bcy1, Tup1, and Mig1. Dicyclomine downregulated Ume6, Ece1, and Pde2 genes which are involved in cAMP signaling pathway and also downregulated the DNA binding protein gene, Rfg1. Dicyclomine significantly upregulated the master negative regulator of hyphal formation, Tup1. Based on this study we suggest that the muscarinic acetylcholine receptor antagonist, dicyclomine could be repositioned as a potential anti-Candida albicans as well as anti-virulence agent.


Assuntos
Candida albicans/efeitos dos fármacos , Diciclomina/farmacologia , Antagonistas Muscarínicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fatores de Virulência/antagonistas & inibidores , Biofilmes/efeitos dos fármacos , Candidíase/microbiologia , AMP Cíclico/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Humanos , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real
10.
Int J Biol Macromol ; 107(Pt B): 2422-2428, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29055706

RESUMO

Lipase is one of the most important groups of enzymes for industry and medicine. It breaks down triacylglycerol to glycerol and fatty acids. Some bacteria use lipase to degrade the extracellular matrix of the host cells to penetrate into the tissues. Dicyclomine is a muscarinic antagonist receptor that relieves the smooth muscle spasm of the gastrointestinal tract and affects the cardiovascular system. In this research, the effect of a dicyclomine on the lipase activity of Pseudomonas aeruginosa was studied. Hanes-Woolf plot showed that the drug inhibited the enzyme by competitive inhibition. The IC50 value (60uM) and Ki (30uM) of the drug revealed that the drug bound to enzyme with high affinity. Determination of enzyme activity in various temperature showed that the maximum activity of lipase was at 60°C both in the presence and absence of the drug. Arrhenius plot determined that the activation energy of the enzyme reaction was increased in the presence of the drug. The model of binding demonstrated that the drug entered a pocket containing 10 amino acids and interacted by hydrogen bond and hydrophobic interaction and the conformational change of the enzyme after binding of the drug was confirmed by fluorescence measurement.


Assuntos
Diciclomina/química , Lipase/química , Pseudomonas aeruginosa/enzimologia , Espasmo/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Diciclomina/farmacologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/fisiopatologia , Humanos , Ligação de Hidrogênio/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Lipase/antagonistas & inibidores , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiopatologia , Pseudomonas aeruginosa/patogenicidade , Espasmo/fisiopatologia , Temperatura
11.
Indian J Pharmacol ; 49(1): 98-101, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28458431

RESUMO

OBJECTIVE: The study was designed to evaluate possible antihistaminic and anticholinergic activities of Equisetum debile. MATERIALS AND METHODS: Effects of crude ethanolic (Ed.Eth) and effects of crude aqueous (Ed.Aq) extracts of E. debile were studied using isolated guinea pig ileum, rabbit jejunum, and rabbit trachea. Tissue responses were recorded using isotonic and isometric transducers, connected with PowerLab data acquisition system. RESULTS: A dose-dependent (0.1-0.3 mg/ml) rightward shift was demonstrated in histamine concentration-response curves. Whereas a complete relaxation of carbachol (1 µM)-induced contractions in isolated rabbit jejunum (3 mg/ml) and tracheal (10 mg/ml) preparations was observed, similar to dicyclomine at 1 and 3 µM, respectively. However, no significant difference between the effects of Ed.Eth and Ed.Aq was observed. CONCLUSION: Study provides pharmacological evidence for the presence of antihistaminic and anticholinergic activities in crude extracts of E. debile and also highlight its medicinal significance in the management of airway and gastrointestinal disorders.


Assuntos
Antagonistas Colinérgicos/farmacologia , Equisetum/química , Antagonistas dos Receptores Histamínicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Antagonistas Colinérgicos/administração & dosagem , Antagonistas Colinérgicos/isolamento & purificação , Diciclomina/administração & dosagem , Diciclomina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Cobaias , Antagonistas dos Receptores Histamínicos/administração & dosagem , Íleo/efeitos dos fármacos , Íleo/metabolismo , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Masculino , Extratos Vegetais/administração & dosagem , Coelhos , Traqueia/efeitos dos fármacos , Traqueia/metabolismo
13.
PLoS One ; 12(1): e0167609, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28052111

RESUMO

OBJECTIVES: We report information about an unpublished 1970s study ("8-way" Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial's findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published. DESIGN: Double blinded, multi-centred, randomized placebo-controlled study. SETTING: 14 clinics in the United States. PARTICIPANTS: 2308 patients in the first 12 weeks of pregnancy with complaints of nausea or vomiting were enrolled. INTERVENTIONS: Each patient was randomized to one of eight arms: placebo, doxylamine/pyridoxine/dicylcomine, doxylamine/pyridoxine, dicylomine/pyridoxine, doxylamine, dicyclomine/pyridoxine, pyridoxine and dicyclomine. Each patient was instructed to take 2 tablets at bedtime and 1 additional tablet in the afternoon or morning if needed, for 7 nights. OUTCOMES: Reported outcomes included the number of hours of nausea reported by patients, the frequency of vomiting reported by patients and the overall efficacy of medication as judged by physicians. RESULTS: Data from 1599 (69% of those randomized) participants were analyzed. Based on the available summary data of physician evaluation of symptoms and ignoring missing data and data integrity issues, the proportion of participants who were "evaluated moderate or excellent" was greater in each of the seven active treatment groups when compared with placebo (57%): doxylamine/pyridoxine/dicylcomine (14% absolute difference versus placebo; 95% CI: 4 to 24), doxylamine/pyridoxine (21; 95% CI 11 to 30), dicylomine/pyridoxine (21; 95% CI 11 to 30), doxylamine (20; 95% CI 10 to 29), dicyclomine/pyridoxine (4; 95% CI -6 to 14), pyridoxine (9; 95% CI -1 to 19) and dicyclomine (4; 95% CI -6 to 14). Based on incomplete information, the most common adverse events were apparently drowsiness and fatigue. There is a high risk of bias in these previously unpublished results given the high attrition rate in a 7 day trial, the lack of prespecified outcomes or analyses, and the exclusion of some data because of questionable data integrity. CONCLUSION: The available information about this "8-way Bendectin" trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias. TRIAL REGISTRATION: Not registered.


Assuntos
Diciclomina/uso terapêutico , Doxilamina/uso terapêutico , Náusea/complicações , Náusea/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Publicações , Piridoxina/uso terapêutico , Vômito/complicações , Vômito/tratamento farmacológico , Comportamento Cooperativo , Diciclomina/efeitos adversos , Doxilamina/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Médicos , Placebos , Gravidez , Viés de Publicação , Piridoxina/efeitos adversos , Relatório de Pesquisa , Risco
14.
Physiol Behav ; 169: 202-207, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27940145

RESUMO

Several studies have investigated the transition of consolidation of recent memory to remote memory in aversively motivated tasks, such as contextual fear conditioning (CFC) and inhibitory avoidance (IA). However, the mechanisms that serve the retrieval of remote memories, has not yet been fully understood. Some evidences suggest that the central cholinergic system appears be involved in the modulation of these processes. Therefore, the present study aimed to investigate the effects of a pre-test administration of dicyclomine, a high-affinity M1 muscarinic receptor antagonist, on the retrieval of remote memories in fear conditioning and IA tasks. Male Wistar rats were trained, and after 1 or 28days, the rats received dicyclomine (16 or 32mg/kg, intraperitoneally, i.p.) and were tested in CFC, tone fear conditioning (TFC) and IA tasks. At both time intervals, 32mg/kg dicyclomine induced impairment of CFC. In TFC task only the performance of the rats 28days after training was impaired. The IA task was not affected in any of the studied intervals. These findings suggest a differential contribution of muscarinic receptors on recent and remote memories retrieval revealing a more generalized role in remote memory.


Assuntos
Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/fisiologia , Medo/fisiologia , Rememoração Mental/fisiologia , Receptor Muscarínico M1/metabolismo , Estimulação Acústica/efeitos adversos , Análise de Variância , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Diciclomina/farmacologia , Relação Dose-Resposta a Droga , Medo/efeitos dos fármacos , Masculino , Rememoração Mental/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Ratos , Ratos Wistar , Fatores de Tempo
15.
Anticancer Drugs ; 28(1): 75-87, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27606721

RESUMO

Recent reports on acetylcholine muscarinic receptor subtype 3 (CHRM3) have shown its growth-promoting role in prostate cancer. Additional studies report the proliferative effect of the cholinergic agonist carbachol on prostate cancer by its agonistic action on CHRM3. This study shows that the type 1 acetylcholine muscarinic receptor (CHRM1) contributes toward the proliferation and growth of prostate cancer. We used growth and cytotoxic assays, the prostate cancer microarray database and CHRM downstream pathways' homology of CHRM subtypes to uncover multiple signals leading to the growth of prostate cancer. Growth assays showed that pilocarpine stimulates the proliferation of prostate cancer. Moreover, it shows that carbachol exerts an additional agonistic action on nicotinic cholinergic receptor of prostate cancer cells that can be blocked by tubocurarine. With the use of selective CHRM1 antagonists such as pirenzepine and dicyclomine, a considerable inhibition of proliferation of prostate cancer cell lines was observed in dose ranging from 15-60 µg/ml of dicyclomine. The microarray database of prostate cancer shows a dominant expression of CHRM1 in prostate cancer compared with other cholinergic subtypes. The bioinformatics of prostate cancer and CHRM pathways show that the downstream signalling include PIP3-AKT-CaM-mediated growth in LNCaP and PC3 cells. Our study suggests that antagonism of CHRM1 may be a potential therapeutic target against prostate cancer.


Assuntos
Neoplasias da Próstata/metabolismo , Receptor Muscarínico M1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Diciclomina/farmacologia , Humanos , Masculino , Pirenzepina/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Muscarínico M1/antagonistas & inibidores , Receptor Muscarínico M1/biossíntese , Receptor Muscarínico M1/genética , Receptor Muscarínico M3/biossíntese , Receptor Muscarínico M3/genética , Receptor Muscarínico M3/metabolismo , Receptores Androgênicos/metabolismo , Transdução de Sinais
16.
BMC Pregnancy Childbirth ; 16(1): 371, 2016 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-27881103

RESUMO

BACKGROUND: Nausea and vomiting of pregnancy (NVP) affects up to 80% of expecting mothers. In April 2013 the FDA approved the delayed-release combination of doxylamine succinate and pyridoxine hydrochloride (Diclegis®) for NVP, based in part, on the results of a phase III randomized trial demonstrating the efficacy of this drug combination [study drug marketed under the trade name Diclectin® in Canada and Diclegis® in the United States] compared to placebo in pregnant women. Study drug dosing occurred for 14 days, which is substantially longer than what has been performed in similar studies. The objective of this study was to evaluate, through secondary analysis, whether the primary measure of efficacy can be demonstrated after five days of treatment. METHODS: Women suffering from NVP were randomized to receive Diclegis® (n = 131) or placebo (n = 125) for 14 days at doses ranging from two to four tablets a day, based on a pre-specified titration protocol. The primary efficacy endpoint was the change in the validated Pregnancy-Unique Quantification of Emesis (PUQE) score at baseline versus Day 15 between Diclegis®-treated and placebo-treated women. For the present study, the change in PUQE score between baseline and Day 15 (end of the study) was compared to the changes observed for Days 3, 4, and 5. RESULTS: The use of delayed-release doxylamine succinate and pyridoxine hydrochloride tablets show improved NVP symptom control as compared to placebo on Days 3,4 and 5, with sustained efficacy until the end of the trial. CONCLUSION: A four day study drug dosing trial with Diclegis® is sufficient to document efficacy, as the results are similar to those achieved after 14 study drug dosing days. The benefit seen at the earlier time validates drug efficacy and minimizes the natural course of improvement. TRIAL REGISTRATION: CTR No. NCT006 14445 2007.


Assuntos
Antieméticos/uso terapêutico , Diciclomina/uso terapêutico , Doxilamina/uso terapêutico , Êmese Gravídica/tratamento farmacológico , Piridoxina/uso terapêutico , Antieméticos/administração & dosagem , Preparações de Ação Retardada , Diciclomina/administração & dosagem , Doxilamina/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Gravidez , Piridoxina/administração & dosagem , Fatores de Tempo
18.
Curr Pain Headache Rep ; 20(5): 31, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27038970

RESUMO

Infantile colic is a self-limiting disorder of excessive infant crying or fussiness that peaks at 6 weeks of age and typically improves by 3 months of age. The etiology of infantile colic has yet to be definitively elucidated, but there is increasing research to support its relationship to migraine. The aims of this review are to present recent research investigating the connection between infantile colic and migraine. The importance of identifying this connection is useful in reducing invasive and potentially harmful investigations and to identify age appropriate pharmacologic interventions that would be safe in this population.


Assuntos
Cólica/tratamento farmacológico , Diciclomina/uso terapêutico , Dietoterapia , Transtornos de Enxaqueca/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Simeticone/uso terapêutico , Cólica/complicações , Cólica/diagnóstico , Humanos , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/diagnóstico
20.
Behav Neurosci ; 130(1): 29-35, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26619084

RESUMO

Extensive research has shown the involvement of the central cholinergic system in the acquisition and consolidation of tasks involving conditioned fear responses, such as those observed in contextual fear conditioning (CFC), tone fear conditioning (TFC) and inhibitory avoidance (IA). However, there are few data concerning the role of this system in the memory retrieval process. Therefore, the present study aimed to compare the effects of the administration of an M1 antagonist on retrieval during these tasks. For each behavioral procedure, groups of male Wistar rats were trained. Twenty-four hr later, they were treated with different doses of dicyclomine (16, 32, or 64 mg/kg, i.p.) or with saline 30 min before the test session. The results showed that dicyclomine at doses of 16 and 32 mg/kg impaired CFC without interfering with IA performance. Moreover, only 64 mg/kg impaired TFC. These data suggest that M1 muscarinic receptors contribute to memory retrieval in CFC and TFC but are not essential for retrieval in IA.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Diciclomina/farmacologia , Emoções/efeitos dos fármacos , Rememoração Mental/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Análise de Variância , Animais , Condicionamento Clássico/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medo/efeitos dos fármacos , Reação de Congelamento Cataléptica/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
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