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1.
Biomed Pharmacother ; 157: 114072, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36493627

RESUMO

Translationally controlled tumor protein (TCTP), a highly conserved protein present in most eukaryotes, is involved in numerous biological processes. Only the dimeric form of TCTP (dTCTP) formed during inflammatory conditions exhibits cytokine-like activity. Therefore, dTCTP is considered as a therapeutic target for allergic diseases. Because monomeric TCTP (mTCTP) and dTCTP share a high topological similarity, we hypothesized that small molecules interacting with mTCTP would also bind to dTCTP and interfere with dTCTP-based cellular processes. In this study, nine compounds listed in the literature as interacting with mTCTP were investigated for their ability to suppress the activity of extracellular dTCTP in bronchial epithelial cells. It was found that one of the nine, meclizine, a piperazine-derivative antihistamine, significantly reduced IL-8 release and suppressed the NF-κB pathway. The direct interaction of meclizine with dTCTP was confirmed by surface plasmon resonance (SPR). Also, we found that meclizine can attenuate ovalbumin (OVA)-induced airway inflammation in mice. Therefore, meclizine might be a potential anti-allergic drug as an inhibitor for dTCTP.


Assuntos
Hipersensibilidade , Proteína Tumoral 1 Controlada por Tradução , Camundongos , Animais , Piperazina/farmacologia , Meclizina/uso terapêutico , Biomarcadores Tumorais/metabolismo , Hipersensibilidade/tratamento farmacológico , Modelos Animais de Doenças , Ovalbumina , Antagonistas dos Receptores Histamínicos/uso terapêutico , Camundongos Endogâmicos BALB C
2.
Biochem Biophys Res Commun ; 592: 87-92, 2022 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-35033871

RESUMO

We screened pre-approved drugs for the survival of the Hu5/KD3 human myogenic progenitors. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, promoted the proliferation and survival of Hu5/KD3 cells. Meclozine increased expression of MyoD, but reduced expression of myosin heavy chain and suppressed myotube formation. Withdrawal of meclozine, however, resumed the ability of Hu5/KD3 cells to differentiate into myotubes. We examined the effects of meclozine on mdx mouse carrying a nonsense mutation in the dystrophin gene and modeling for Duchenne muscular dystrophy. Intragastric administration of meclozine in mdx mouse increased the body weight, the muscle mass in the lower limbs, the cross-sectional area of the paravertebral muscle, and improved exercise performances. Previous reports show that inhibition of phosphorylation of ERK1/2 improves muscle functions in mouse models for Emery-Dreifuss muscular dystrophy and cancer cachexia, as well as in mdx mice. We and others previously showed that meclozine blocks the phosphorylation of ERK1/2 in cultured cells. We currently showed that meclozine decreased phosphorylation of ERK1/2 in muscles in mdx mice but not in wild-type mice. This was likely to be one of the underlying mechanisms of the effects of meclozine on mdx mice.


Assuntos
Meclizina/farmacologia , Força Muscular/fisiologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Masculino , Meclizina/uso terapêutico , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Atividade Motora/efeitos dos fármacos , Desenvolvimento Muscular/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Distrofia Muscular de Duchenne/tratamento farmacológico , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/fisiopatologia , Fosforilação/efeitos dos fármacos
3.
J Assoc Res Otolaryngol ; 22(5): 527-549, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34009490

RESUMO

Management of vestibular dysfunction may include treatment with medications that are thought to act to suppress vestibular function and reduce or eliminate abnormal sensitivity to head motions. The extent to which vestibular medications act centrally or peripherally is still debated. In this study, two commonly prescribed medications, meclizine and diazepam, and a candidate for future clinical use, JNJ7777120, were evaluated for their effects on short latency compound action potentials generated by the peripheral vestibular system and corresponding central neural relays (i.e., vestibular sensory-evoked potentials, VsEPs). The effects of the selected drugs developed slowly over the course of two hours in the mouse. Findings indicate that meclizine (600 mg/kg) and diazepam (> 60 mg/kg) can act on peripheral elements of the vestibular maculae whereas diazepam also acts most effectively on central gravity receptor circuits to exert its suppressive effects. The novel pharmacological agent JNJ7777120 (160 mg/kg) acts in the vestibular periphery to enhance macular responses to transient stimuli (VsEPs) while, hypothetically, suppressing macular responses to sustained or slowly changing stimuli.


Assuntos
Diazepam/farmacologia , Indóis/farmacologia , Meclizina/farmacologia , Piperazinas/farmacologia , Sistema Vestibular/efeitos dos fármacos , Animais , Diazepam/uso terapêutico , Indóis/uso terapêutico , Meclizina/uso terapêutico , Camundongos , Piperazinas/uso terapêutico , Vestíbulo do Labirinto
4.
Can J Physiol Pharmacol ; 98(6): 383-390, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31935134

RESUMO

Pregnane X receptors (PXRs) regulate the expression of ATP-binding cassette proteins transporters and organic anion transporting polypeptides responsible for influx/efflux of xenobiotics across the brain. Ligand activation of PXR augments the expression of P-gp and promotes amyloid-ß clearance across the blood-brain barrier. Dementia was induced in mice by intacerebroventricular administration of streptozotocin (STZ) followed by treatment with meclizine, a PXR agonist, and subsequently exposed to the Morris water maze test and biochemical and histopathological analysis to evaluate the effect on cognition. STZ-treated mice exhibited significant enhancement in brain thiobarbituric acid reactive species, interleukin-1ß, tumour necrosis factor-α, myeloperoxidase, and acetylcholinestrase activity in addition to diminution in glutathione levels and superoxide dismutase activity in comparison to untreated mice. Administration of meclizine to STZ mice recuperated cognition and biochemical alterations. Concomitant administration of ketoconazole, a PXR antagonist, with meclizine prevented the protective effects. The upshots of our study proclaim that meclizine protects cognitive deficits by virtue of its antioxidant, anticholinesterase, and antiinflammatory properties. Results also signify the potential of PXR in neuroprotective actions of meclizine in dementia.


Assuntos
Demência/induzido quimicamente , Demência/complicações , Meclizina/farmacologia , Transtornos da Memória/complicações , Transtornos da Memória/tratamento farmacológico , Receptor de Pregnano X/metabolismo , Estreptozocina/administração & dosagem , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Feminino , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Masculino , Meclizina/uso terapêutico , Transtornos da Memória/metabolismo , Camundongos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
Scand J Prim Health Care ; 37(1): 30-40, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30822254

RESUMO

OBJECTIVE: Hyperemesis gravidarum (HG) affects 0.3-3% of pregnant women and is a leading cause of hospitalization in early pregnancy. The aim of the study was to investigate women's treatment and management of HG, as well as the consequences of HG on women's daily life. DESIGN AND SETTING: A cross-sectional study based on a structured telephone interview and an online questionnaire. Participants were recruited by social media and by the Norwegian patient's organization for HG. SUBJECTS: Norwegian women that experienced HG. MAIN OUTCOME MEASURE: Women's perspectives on management and consequences of HG. RESULTS: The study included 107 women. Maternal morbidity was profound; about 3/4 of participants were hospitalized due to HG, and the majority showed clinical signs of dehydration (79%), ketonuria (75%), and >5% weight loss (84%). Antiemetics were used by >90% and frequently prescribed "as needed". Metoclopramide (71%) and meclozine (51%) were most commonly used. Participants described HG as having severe psychosocial consequences and profound impact on daily activities. Almost two out of five reported thoughts of elective abortion, and 8 women had at least one elective pregnancy termination due to HG. Overall, 20 women (19%) changed GPs due to dissatisfaction with HG management. CONCLUSION: Despite the high psychosocial burden and major impact on daily activities, many women with HG reported a lack of support from healthcare professionals and suboptimal management. Greater awareness and knowledge among healthcare professionals is needed to improve care for women with HG. Key Points There is a paucity of studies on management and the consequences of HG on women's daily lives and psychosocial burden. We found that: • Many women described HG as one of their worst life experiences with profound morbidity. • Many women reported suboptimal management of HG and lack of support from healthcare professionals. • Greater understanding of patient perspectives among healthcare professionals is important to improve care and management for HG patients.


Assuntos
Atividades Cotidianas , Atitude , Hiperêmese Gravídica , Náusea/terapia , Gestantes , Qualidade de Vida , Aborto Induzido , Adulto , Antieméticos/uso terapêutico , Estudos Transversais , Desidratação/complicações , Desidratação/epidemiologia , Emoções , Feminino , Hospitalização , Humanos , Hiperêmese Gravídica/complicações , Hiperêmese Gravídica/psicologia , Hiperêmese Gravídica/terapia , Cetose/complicações , Cetose/epidemiologia , Meclizina/uso terapêutico , Metoclopramida/uso terapêutico , Náusea/complicações , Náusea/psicologia , Noruega/epidemiologia , Satisfação do Paciente , Gravidez , Gestantes/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Redução de Peso
7.
Am J Phys Med Rehabil ; 96(8): e151-e154, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28081025

RESUMO

Sialorrhea in children with cerebral palsy (CP) results in aspiration, decreased social integration, and poor quality of life. Management options include transdermal anticholinergics such as the scopolamine patch. A controlled clinical trial has proven botulinum toxin (BTX) injections into the salivary glands are an effective alternative to transdermal anticholinergics with a safer side effect profile. Multiple studies of the injections in diverse populations demonstrate reduction in saliva production with improvement in quality of life and decrease in hospitalization-associated costs. The authors describe a 15-year-old boy with spastic quadriplegic CP who developed emesis, nausea, and lethargy 1 day after the first injection of botulinum toxin A (BTX-A) to his salivary glands for sialorrhea management. The authors ascribed his symptoms to scopolamine withdrawal. Given the lack of exposure in the medical literature, there is minimal awareness of the withdrawal syndrome from transdermal scopolamine in children with or without CP, resulting in delayed diagnosis and potential complications. Treatment of the withdrawal syndrome has been successful with meclizine though safety and efficacy has not been established in children younger than 12 despite frequent clinical and over-the-counter use. Prompt diagnosis of the transdermal scopolamine withdrawal syndrome can result in quicker treatment and a shorter hospital stay.


Assuntos
Paralisia Cerebral/complicações , Diagnóstico Tardio/efeitos adversos , Escopolamina/efeitos adversos , Sialorreia/tratamento farmacológico , Síndrome de Abstinência a Substâncias/diagnóstico , Adolescente , Antieméticos/uso terapêutico , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Paralisia Cerebral/tratamento farmacológico , Humanos , Injeções Subcutâneas , Letargia/induzido quimicamente , Masculino , Meclizina/uso terapêutico , Náusea/induzido quimicamente , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/efeitos adversos , Glândulas Salivares , Escopolamina/administração & dosagem , Sialorreia/etiologia , Síndrome de Abstinência a Substâncias/complicações , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adesivo Transdérmico , Resultado do Tratamento , Vômito/induzido quimicamente
8.
J Emerg Med ; 52(1): 23-27, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27789115

RESUMO

BACKGROUND: Vertigo is a debilitating disease that is commonly encountered in the emergency department (ED). Diazepam and meclizine are oral medications that are commonly used to alleviate symptoms. OBJECTIVES: We sought to determine whether meclizine or diazepam is superior in the treatment of patients with peripheral vertigo in the ED. METHODS: We performed a double-blind clinical trial at a suburban, teaching ED. We randomized a convenience sample of adult patients with acute peripheral vertigo (APV) to diazepam 5 mg or meclizine 25 mg orally. Demographic and historical features were recorded on a standardized data form. Patients recorded their initial level (t0) of vertigo on a 100-mm visual analog scale (VAS) and after 30 min (t30) and 60 min (t60). The primary outcome parameter was the mean change in VAS score from t0 to t60. Differences between groups and 95% confidence intervals were calculated. Our a priori power calculation estimated that a sample size of 20 patients in each group was required to have an 80% power to detect a difference of 20 mm between treatment groups. RESULTS: There were 20 patients in the diazepam group and 20 in the meclizine group. The two groups were similar with respect to patient demographics and presenting signs and symptoms. At t60, the mean improvements in the diazepam and meclizine groups were 36 and 40, respectively (difference -4; 95% confidence interval -20 to 12; p = 0.60). CONCLUSION: We found no difference between oral diazepam and oral meclizine for the treatment of ED patients with acute peripheral vertigo.


Assuntos
Diazepam/farmacologia , Meclizina/farmacologia , Resultado do Tratamento , Vertigem/tratamento farmacológico , Adulto , Diazepam/uso terapêutico , Método Duplo-Cego , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Meclizina/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos
9.
J Spec Oper Med ; 16(2): 78-81, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27450607

RESUMO

The series objective is to review various clinical conditions/ presentations, including the latest evidence on management, and to dispel common myths. In the process, core knowledge and management principles are enhanced. A clinical case will be presented. Cases will be drawn from real life but phrased in a context that is applicable to the Special Operations Forces (SOF) or tactical emergency medical support (TEMS) environment. Details will be presented in such a way that the reader can follow along and identify how they would manage the case clinically depending on their experience and environment situation. Commentary will be provided by currently serving military medical technicians. The medics and author will draw on their SOF experience to communicate relevant clinical concepts pertinent to different operational environments including SOF and TEMS. Commentary and input from active special op.


Assuntos
Acupressão/métodos , Antieméticos/uso terapêutico , Antagonistas Colinérgicos/uso terapêutico , Antagonistas de Dopamina/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Enjoo devido ao Movimento/prevenção & controle , Auxiliares de Emergência , Humanos , Meclizina/uso terapêutico , Metoclopramida/uso terapêutico , Militares , Enjoo devido ao Movimento/fisiopatologia , Enjoo devido ao Movimento/terapia , Ondansetron/uso terapêutico , Prometazina/uso terapêutico , Escopolamina/uso terapêutico
10.
Nat Rev Dis Primers ; 2: 16028, 2016 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-27170253

RESUMO

Meniere's disease (MD) is a disorder of the inner ear that causes vertigo attacks, fluctuating hearing loss, tinnitus and aural fullness. The aetiology of MD is multifactorial. A characteristic sign of MD is endolymphatic hydrops (EH), a disorder in which excessive endolymph accumulates in the inner ear and causes damage to the ganglion cells. In most patients, the clinical symptoms of MD present after considerable accumulation of endolymph has occurred. However, some patients develop symptoms in the early stages of EH. The reason for the variability in the symptomatology is unknown and the relationship between EH and the clinical symptoms of MD requires further study. The diagnosis of MD is based on clinical symptoms but can be complemented with functional inner ear tests, including audiometry, vestibular-evoked myogenic potential testing, caloric testing, electrocochleography or head impulse tests. MRI has been optimized to directly visualize EH in the cochlea, vestibule and semicircular canals, and its use is shifting from the research setting to the clinic. The management of MD is mainly aimed at the relief of acute attacks of vertigo and the prevention of recurrent attacks. Therapeutic options are based on empirical evidence and include the management of risk factors and a conservative approach as the first line of treatment. When medical treatment is unable to suppress vertigo attacks, intratympanic gentamicin therapy or endolymphatic sac decompression surgery is usually considered. This Primer covers the pathophysiology, symptomatology, diagnosis, management, quality of life and prevention of MD.


Assuntos
Doença de Meniere/complicações , Doença de Meniere/fisiopatologia , Antieméticos/farmacologia , Antieméticos/uso terapêutico , Audiometria/métodos , Benzodiazepinas/farmacologia , Benzodiazepinas/uso terapêutico , Ablação por Cateter/métodos , Dimenidrinato/farmacologia , Dimenidrinato/uso terapêutico , Orelha Interna/patologia , Orelha Interna/fisiopatologia , Endolinfa/metabolismo , Gânglios Sensitivos/anormalidades , Gânglios Sensitivos/lesões , Perda Auditiva/etiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Meclizina/farmacologia , Meclizina/uso terapêutico , Doença de Meniere/epidemiologia , Prometazina/farmacologia , Prometazina/uso terapêutico , Qualidade de Vida/psicologia , Zumbido/etiologia , Vertigem/etiologia
11.
EBioMedicine ; 2(9): 1090-101, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26501107

RESUMO

Global or local ischemia contributes to the pathogenesis of acute kidney injury (AKI). Currently there are no specific therapies to prevent AKI. Potentiation of glycolytic metabolism and attenuation of mitochondrial respiration may decrease cell injury and reduce reactive oxygen species generation from the mitochondria. Meclizine, an over-the-counter anti-nausea and -dizziness drug, was identified in a 'nutrient-sensitized' chemical screen. Pretreatment with 100 mg/kg of meclizine, 17 h prior to ischemia protected mice from IRI. Serum creatinine levels at 24 h after IRI were 0.13 ± 0.06 mg/dl (sham, n = 3), 1.59 ± 0.10 mg/dl (vehicle, n = 8) and 0.89 ± 0.11 mg/dl (meclizine, n = 8). Kidney injury was significantly decreased in meclizine treated mice compared with vehicle group (p < 0.001). Protection was also seen when meclizine was administered 24 h prior to ischemia. Meclizine reduced inflammation, mitochondrial oxygen consumption, oxidative stress, mitochondrial fragmentation, and tubular injury. Meclizine preconditioned kidney tubular epithelial cells, exposed to blockade of glycolytic and oxidative metabolism with 2-deoxyglucose and NaCN, had reduced LDH and cytochrome c release. Meclizine upregulated glycolysis in glucose-containing media and reduced cellular ATP levels in galactose-containing media. Meclizine inhibited the Kennedy pathway and caused rapid accumulation of phosphoethanolamine. Phosphoethanolamine recapitulated meclizine-induced protection both in vitro and in vivo.


Assuntos
Precondicionamento Isquêmico , Rim/irrigação sanguínea , Rim/patologia , Meclizina/uso terapêutico , Substâncias Protetoras/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Injúria Renal Aguda/complicações , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Trifosfato de Adenosina/metabolismo , Animais , Respiração Celular/efeitos dos fármacos , Citocromos c/metabolismo , Desoxiglucose/farmacologia , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Etanolaminas/metabolismo , Galactose/farmacologia , Glicólise/efeitos dos fármacos , Humanos , Inflamação/complicações , Inflamação/patologia , Rim/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , L-Lactato Desidrogenase/metabolismo , Células LLC-PK1 , Masculino , Meclizina/farmacologia , Meclizina/toxicidade , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia , Cianeto de Sódio/farmacologia , Suínos , Regulação para Cima/efeitos dos fármacos
12.
Rev cuba neurol neurocir ; 5(2)jul. 2015. ilus
Artigo em Espanhol | CUMED | ID: cum-76218

RESUMO

Introducción: La disección de las arterias carótidas y vertebrales representa una causa rara de ictus, y su mayor incidencia se reporta en los pacientes jóvenes y en la edad media de la vida. La presentación de este caso tiene como objetivo mostrar la variedad de manifestaciones clínicas de la disección de la arteria vertebral y algunos de los problemas actuales en su manejo.Caso clínico: Paciente masculino de 42 años que luego de un giro brusco de la cabeza comenzó con un cuadro de mareos que mejoraban con el decúbito y se exacerbaban con los cambios de posición. En la exploración neurológica se encontraron signos de focalización neurológica como ataxia de la marcha, dismetría, disdiadococinesia, hipotonía muscular derecha, y paresia del músculo recto lateral derecho por afectación del VI nervio craneal. En las imágenes de resonancia magnética se encontró un infarto en el hemisferio cerebeloso derecho y la angioTAC multicorte de cráneo permitió observar los signos de la disección de la arteria vertebral derecha. Se decidió el ingreso en la sala de Neurología con el diagnóstico de ictus isquémico del territorio posterior de causa inhabitual. Se comenzótratamiento con aspirina (125 mg/día). A los 10 días de evolución comenzó con mejoría importante y paulatinamente ocurrió la desaparición de los síntomas focales neurológicos.Conclusiones: Este caso de disección arterial reafirma la necesidad de considerar esta entidad como causa de ictus isquémico en el adulto joven. La atribución de los síntomas a procesos menos graves y la variabilidad de los síntomas enseñan que al interrogar yexaminar a un paciente se requiere de gran pericia y de la correlación neuroanatómica y cronológica de los hallazgos. Asimismo, es fundamental un diagnóstico rápido y el inicio precoz de una terapia con el potencial de cambiar el curso de esta entidad(AU)


Introduction: Carotid and vertebral arteries dissection represents a rare cause of stroke, and it´s reported mainly in young and middle age patients. This case shows the variable resentation of vertebral artery dissection and some current management problems.Clinical case: 42-year-old male patient who began in the morning after a sudden head rotation with dizziness that improved with decubitus and were exacerbated with the changes of position. Neurological examination revealed focal signs as ataxic gait, dysmetria, dysdiadochokinesis, right muscle hypotonia, and paresis of right abducens muscle due cranial nerve VI lesion. Magnetic resonance imagesshowed an infarct in right cerebellar hemisphere and angioCT scan showed right vertebral artery dissection. It was decided hospitalization in neurology service with diagnosis of ischemic stroke of posterior territory. Then the patient received treatment with aspirin (125 mg/day).After 10 days of evolution, he began with improvement of the neurological focal symptoms, and later with disappearance of neurological signs.Conclusions: This case reaffirms the need to consider this entity as cause of ischemic stroke in young adults. The attribution of symptoms to minor conditions and symptoms variability teach the value of capacity for history collection and examination, anatomic correlation and chronologic approach. Also, is fundamental a rapid diagnosis and the early beginning of therapy, that can potentially change the evolutionof this entity(AU)


Assuntos
Humanos , Masculino , Adulto , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Dissecação da Artéria Vertebral/complicações , Lesões do Pescoço/tratamento farmacológico , Meclizina/administração & dosagem , Meclizina/uso terapêutico , Acetaminofen/administração & dosagem , Acetaminofen/uso terapêutico
13.
Endocrinology ; 156(2): 548-54, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25456072

RESUMO

Achondroplasia (ACH) is one of the most common skeletal dysplasias causing short stature owing to a gain-of-function mutation in the FGFR3 gene, which encodes the fibroblast growth factor receptor 3. We found that meclozine, an over-the-counter drug for motion sickness, inhibited elevated FGFR3 signaling in chondrocytic cells. To examine the feasibility of meclozine administration in clinical settings, we investigated the effects of meclozine on ACH model mice carrying the heterozygous Fgfr3(ach) transgene. We quantified the effect of meclozine in bone explant cultures employing limb rudiments isolated from developing embryonic tibiae from Fgfr3(ach) mice. We found that meclozine significantly increased the full-length and cartilaginous primordia of embryonic tibiae isolated from Fgfr3(ach) mice. We next analyzed the skeletal phenotypes of growing Fgfr3(ach) mice and wild-type mice with or without meclozine treatment. In Fgfr3(ach) mice, meclozine significantly increased the body length after 2 weeks of administration. At skeletal maturity, the bone lengths including the cranium, radius, ulna, femur, tibia, and vertebrae were significantly longer in meclozine-treated Fgfr3(ach) mice than in untreated Fgfr3(ach) mice. Interestingly, meclozine also increased bone growth in wild-type mice. The plasma concentration of meclozine during treatment was within the range that has been used in clinical settings for motion sickness. Increased longitudinal bone growth in Fgfr3(ach) mice by oral administration of meclozine in a growth period suggests potential clinical feasibility of meclozine for the improvement of short stature in ACH.


Assuntos
Acondroplasia/tratamento farmacológico , Desenvolvimento Ósseo/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Meclizina/uso terapêutico , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Acondroplasia/genética , Animais , Feminino , Antagonistas dos Receptores Histamínicos H1/sangue , Antagonistas dos Receptores Histamínicos H1/farmacologia , Técnicas In Vitro , Masculino , Meclizina/sangue , Meclizina/farmacologia , Camundongos Transgênicos , Mutação , Distribuição Aleatória , Tíbia/crescimento & desenvolvimento
14.
Audiol Neurootol ; 17(4): 235-42, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22517315

RESUMO

INTRODUCTION: Sensory conflicts in the vestibular system lead to motion sickness of which space motion sickness (SMS) is a special case. SMS affects up to 70% of the astronauts during the first 3 days in space. The search for effective countermeasures has led to several nonpharmacological and pharmacological approaches. The current study focuses on the effects of lorazepam (1 mg), meclizine (25 mg), promethazine (25 mg), and scopolamine (0.4 mg) on the vestibular system, with special focus on the canal and otolith functions separately. METHODS: The study had a placebo-controlled, single blind, repeated measures design. Sixteen healthy volunteers were subjected to a total of 7 test sessions, the first and last being without intake of medication. Semicircular canal function was evaluated by means of electronystagmography and otolith function with unilateral centrifugation. The horizontal semicircular canal function was characterized by the vestibulo-ocular reflex (VOR) gain measured during earth vertical axis rotation as well as the total caloric response. The function of the utricles was represented by the utricular sensitivity, reflecting the ocular counter roll relative to the virtual induced head tilt. RESULTS: Promethazine significantly decreased the semicircular canal and utricular parameters. Both scopolamine and lorazepam caused only a decrease in the utricular sensitivity, whereas meclizine only decreased the semicircular canal-induced VOR gain. DISCUSSION: The results show that the drugs affected different areas of the vestibular system and that the effects can thus be attributed to the specific pharmacological properties of each drug. Meclizine, as an antihistaminergic and weak anticholinergic drug, only affected the VOR gain, suggesting a central action on the medial vestibular nucleus. The same site of action is suggested for the anticholinergic scopolamine since acetylcholine receptors are present and utricular fibers terminate here. The global vestibular suppression caused by promethazine is probably a consequence of its anticholinergic, antihistaminergic, and antidopaminergic properties. Based on the fact that lorazepam increased the affinity of gamma-aminobutyric acid (GABA) for the GABA(A)-receptor and its effects on the utriculi, the site of action seems to be the lateral vestibular nucleus. CONCLUSION: Meclizine, scopolamine, and lorazepam selectively suppress specific parts of the vestibular system. Selective suppression of different parts of the vestibular system may be more beneficial for alleviating (space) motion sickness than general suppressive agents. Additionally, this knowledge may help the clinician in his therapeutic management of patients with either semicircular canal or otolith dysfunction.


Assuntos
Antieméticos/farmacologia , Reflexo Vestíbulo-Ocular/efeitos dos fármacos , Sáculo e Utrículo/efeitos dos fármacos , Canais Semicirculares/efeitos dos fármacos , Enjoo devido ao Movimento em Voo Espacial/prevenção & controle , Adulto , Antieméticos/uso terapêutico , Feminino , Humanos , Lorazepam/farmacologia , Lorazepam/uso terapêutico , Masculino , Meclizina/farmacologia , Meclizina/uso terapêutico , Pessoa de Meia-Idade , Prometazina/farmacologia , Prometazina/uso terapêutico , Reflexo Vestíbulo-Ocular/fisiologia , Sáculo e Utrículo/fisiopatologia , Escopolamina/farmacologia , Escopolamina/uso terapêutico , Canais Semicirculares/fisiopatologia , Enjoo devido ao Movimento em Voo Espacial/tratamento farmacológico , Enjoo devido ao Movimento em Voo Espacial/fisiopatologia , Testes de Função Vestibular
15.
Hum Mol Genet ; 20(2): 294-300, 2011 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-20977989

RESUMO

Defects in cellular energy metabolism represent an early feature in a variety of human neurodegenerative diseases. Recent studies have shown that targeting energy metabolism can protect against neuronal cell death in such diseases. Here, we show that meclizine, a clinically used drug that we have recently shown to silence oxidative metabolism, suppresses apoptotic cell death in a murine cellular model of polyglutamine (polyQ) toxicity. We further show that this protective effect extends to neuronal dystrophy and cell death in Caenorhabditis elegans and Drosophila melanogaster models of polyQ toxicity. Meclizine's mechanism of action is not attributable to its anti-histaminergic or anti-muscarinic activity, but rather, strongly correlates with its ability to suppress mitochondrial respiration. Since meclizine is an approved drug that crosses the blood-brain barrier, it may hold therapeutic potential in the treatment of polyQ toxicity disorders, such as Huntington's disease.


Assuntos
Doença de Huntington/tratamento farmacológico , Meclizina/farmacologia , Meclizina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Modelos Animais de Doenças , Drosophila melanogaster/efeitos dos fármacos , Humanos , Proteína Huntingtina , Doença de Huntington/metabolismo , Camundongos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Peptídeos/efeitos adversos
16.
Am J Health Syst Pharm ; 66(22): 2024-6, 2009 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-19890085

RESUMO

PURPOSE: The case of a patient who treated withdrawal symptoms from trans-dermal scopolamine with meclizine is reported. SUMMARY: A 30-year-old woman for whom transdermal scopolamine was prescribed to manage motion sickness during a vacation experienced severe withdrawal symptoms that began 24 hours after patch removal and lasted for several days. Other medications included an oral contraceptive and as-needed zolmitriptan for migraines. She used the scopolamine patches as prescribed, applying one patch behind the ear every 3 days. After 10 consecutive days of wearing the patch and experiencing no motion sickness, she began to develop dry mouth and uncomfortable, dry eyes, which prompted her to remove the patch. After 24 hours without the patch, she developed severe nausea that did not subside during a car ride. Due to the intractable nausea, she applied a new patch, which she wore for 3 consecutive days without recurrence of the nausea. Upon returning from the trip, she removed the last patch. Twelve hours after the last patch was removed, nausea recurred but was not related to motion. She felt better while lying down, but felt nauseated when standing or walking. After 3 days of this nausea, she began taking nonprescription meclizine 25 mg orally every 12 hours. The nausea subsided after two doses, and she was able to resume her normal activities. The nausea did not recur after discontinuation of the meclizine. She had used transdermal scopolamine eight years prior without any withdrawal symptoms. CONCLUSION: Withdrawal symptoms experienced after removal of a transdermal scopolamine patch were successfully treated with oral meclizine.


Assuntos
Antagonistas Muscarínicos/efeitos adversos , Escopolamina/efeitos adversos , Síndrome de Abstinência a Substâncias/etiologia , Administração Cutânea , Adulto , Antieméticos/uso terapêutico , Feminino , Humanos , Meclizina/uso terapêutico , Enjoo devido ao Movimento/prevenção & controle , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/uso terapêutico , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Escopolamina/administração & dosagem , Índice de Gravidade de Doença , Síndrome de Abstinência a Substâncias/tratamento farmacológico
17.
Aviat Space Environ Med ; 78(4): 408-13, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17484344

RESUMO

INTRODUCTION: Despite many existing treatments, airsickness is an issue of concern for soldiers being transported by helicopter. This experiment examined the efficacy of four airsickness treatments and their effects on performance. This study replicated the transport of soldiers in the cabin of an UH-60 Black Hawk helicopter performing many of the flight maneuvers potentially experienced in a night troop transport during turbulent conditions. METHODS: A double-blinded, placebo-controlled design was used to compare the effectiveness of four airsickness countermeasures to their placebo controls. There were 64 male, non-aviator subjects (ages 18-34 yr) who were recruited for the study. Of these, 16 subjects were randomly assigned to each of 4 groups: (1) promethazine (25 mg) + caffeine (200 mg); (2) meclizine (25 mg); (3) Scopolamine patch (1.5 mg); and 4) acustimulation wristband. Each individual participated twice, once with the treatment and once with placebo. RESULTS: The findings indicated that only the combination of promethazine + caffeine showed a statistically significant reduction in nausea and motion sickness severity, and an improvement in reaction time when compared with its placebo control. DISCUSSION: Data from this study indicated that of the countermeasures tested, promethazine + caffeine was the most effective at reducing airsickness while producing the fewest side effects when compared with its placebo. In addition, this study demonstrated that over-the-counter caffeine can serve as an effective stimulant counterpart to promethazine. This may be a more appealing option than employing scheduled sympathomimetic drugs in a combat environment.


Assuntos
Aeronaves , Antieméticos/uso terapêutico , Meclizina/uso terapêutico , Medicina Militar , Militares , Enjoo devido ao Movimento/prevenção & controle , Prometazina/uso terapêutico , Escopolamina/uso terapêutico , Estimulação Acústica , Adolescente , Adulto , Inquéritos Epidemiológicos , Humanos , Masculino , Antagonistas Muscarínicos/uso terapêutico , Inquéritos e Questionários
18.
AANA J ; 75(1): 27-33, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17304780

RESUMO

Postoperative nausea and vomiting (PONV) is prevalent in surgical patients with known risk factors: general anesthesia, female, nonsmoker, motion sickness history, and PONV history. Common treatment involves ondansetron; however, the effects are short-lived, and supplemental medication may be required. Meclizine, a long-acting drug with a low side-effect profile, may be ideal in combination with ondansetron for at-risk patients. We randomized 77 subjects scheduled for general anesthesia and screened for 4 of 5 PONV risk factors for experimental or control group assignment. Severity of PONV was measured using a 0 to 10 verbal numeric rating scale (VNRS). Other measured variables included time to onset and incidence of PONV and total antiemetic requirements. No significant differences in demographics (excluding weight), surgical or anesthesia time, analgesic requirements, or nausea incidence in the postanesthesia care unit (PACU) and same-day surgery unit were noted. The meclizine group had lower VNRS scores in the PACU at 15 (P = .013) and 45 (P = .006) minutes following rescue treatment. The incidence of nausea was lower in the meclizine vs. placebo group (10% vs. 29%) following discharge (P = .038). Prophylactic meclizine resulted in lower incidence and severity of PONV in a high-risk population, especially after rescue treatment.


Assuntos
Meclizina/uso terapêutico , Náusea/prevenção & controle , Ondansetron/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Vômito/prevenção & controle , Adulto , Quimioterapia Combinada , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enjoo devido ao Movimento/epidemiologia , Medição de Risco
19.
In. Ministerio de Salud Pública.Centro para el desarrollo de la Farmacoepidemiología. Formulario Nacional de Medicamentos. La Habana, Ecimed, 2006. .
Monografia em Espanhol | CUMED | ID: cum-44167
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