Efficacy and safety of tolperisone versus baclofen among Chinese patients with spasticity associated with spinal cord injury: a non-randomized retrospective study

There are many medications available to treat spasticity, but the tolerability of medications is the main issue for choosing the best treatment. The objectives of this study were to compare the efficacy and adverse effects of tolperisone compared to baclofen among patients with spasticity associated with spinal cord injury. Patients received baclofen plus physical therapy (BAF+PT, n=135) or tolperisone plus physical therapy (TOL+PT, n=116), or physical therapy alone (PT, n=180). The modified Ashworth scale score, the modified Medical Research Council score, the Barthel Index score, and the Disability Assessment scale score were improved (P<0.05 for all) in all the patients at the end of 6 weeks compared to before interventions. After 6 weeks, the overall coefficient of efficacy of the intervention(s) in the BAF+PT, TOL+PT, and PT groups were 1.15, 0.45, and 0.05, respectively. The patients of the BAF+PT group reported asthenia, drowsiness, and sleepiness and those of the TOL+PT group reported dyspepsia and epigastric pain as adverse effects. When comparing drug interventions to physical therapy alone, both baclofen plus physical therapy and tolperisone plus physical therapy played a significant role in the improvement of daily activities of patients. Nonetheless, baclofen plus physical therapy was tentatively effective. Tolperisone plus physical therapy was slightly effective. In addition, baclofen caused adverse effects related to the sedative manifestation (Level of Evidence: III; Technical Efficacy Stage: 4).

Síndrome de persona rígida: presentación de caso clínico y abordaje terapéutico / Stiff man Syndrome Clinical case presentation and therapeutic approach

Introducción: El síndrome del hombre rígido representa una rara enfermedad neuromuscular caracterizada por rigidez muscular progresiva y espasmos musculares dolorosos que afecta a 1 persona por cada millón de habitantes por año en el mundo. En la mayoría de los pacientes se encuentran niveles elevados de anticuerpos descarboxilasa del ácido glutámico. En Colombia solo se han publicado alrededor de 3 casos, lo que motiva la presentación de un nuevo informe que aporte a la discusión actual en el campo de la neurología clínica. Caso clínico: Paciente de sexo femenino de 35 años con cuadro clínico progresivo de varios años, caracterizado por contracciones paroxísticas dolorosas, parestesias y pérdida de fuerza. Se documentó la presencia de anticuerpos anti-GAD compatibles con el síndrome del hombre rígido. Tras un tratamiento integral, que incluyó la infusión farmacológicamente intratecal con baclofeno, se obtuvo mejoría clínica en el índice de Barthel. Conclusiones: El síndrome del hombre rígido es una condición infradiagnosticada que se asocia a un deterioro de la calidad de vida de quienes lo padecen.

Introduction: Stiff man syndrome represents a rare neuromuscular disease characterized by progressive muscle rigidity and painful muscle spasms that affects 1 person for every million habitants per year in the world. High levels of glutamic acid antibodies decarboxylase are found in most patients. In Colombia, only around 3 cases have been published, which motivates the presentation of a new report that contributes to the current discussion in the field of clinical neurology. Clinical Case: 35-year-old female patient with a progressive clinical picture of several years, characterized by painful paroxysmal contractions, paresthesias and loss of strength. The presence of anti-GAD antibodies was documented, compatible with Stiff man syndrome. After comprehensive treatment, which included pharmacologically intrathecal infusion with baclofen, clinical improvement was obtained in the Barthel index. Conclusions: Stiff man syndrome is an underdiagnosed condition which is associated with a deterioration in the quality of life for those who suffer from it.

Aicardi syndrome: a case report / Síndrome de Aicardi: relato de caso

Abstract Introduction: the Aicardi syndrome (SA) is characterized as a rare syndrome identified in the presence of three classic characteristics: corpus callosum agenesis, chorioretinal lacunaeand infantile spasms. Description: data collection involved information reported by the mother and the accompanying physiotherapist describing the patient's clinical history andmajor complications according to clinical evolution, treatment, and therapeutic response. At two months of age, the child presented a delayed neuropsychomotor development and infantile spasms.However,the diagnosis of the syndrome was only performed at six months of life, involving brain magnetic resonance imaging where corneal body agenesis was observed. A multidisciplinary treatment was assembledwith a neuropediatrician, a physiotherapist, a psychologist, a nutritionistand a speech therapist, besides drug treatment with baclofen and phenobarbital. Discussion: through the established treatment, the child displayedmotor gain, cervical control, improvement of the respiratory condition, and no need forhospital admissions;these outcomescharacterizea good clinical evolution associated with the physiotherapeutic intervention focused on prevention and minimization of respiratory alterationsthatare frequently associated with morbidity and mortality in these cases. The results obtained point out the fundamental role of multidisciplinary intervention in coping with this condition.

Resumo Introdução: a Síndrome de Aicardi (SA), caracteriza-se como uma síndrome rara identificada na presença das três características clássicas: agenesia de corpo caloso, lacunas coriorretinianas e espamos infantis. Descrição: a coleta de dados envolveu informações relatadas pela genitora e pelo fisioterapeuta acompanhante da paciente, descrevendo assim a história clínica da paciente, as principais complicações de acordo com a evolução clínica, o tratamento e resposta terapêutica. Aos dois meses de idade a criança apresentou atraso no desenvolvimento neuropsicomotor e espasmos infantis, porém o diagnóstico da síndrome foi realizado somente aos seis meses de vida envolvendo um exame de ressonância magnética de encéfalo onde foi observada agenesia de corpo caloso, iniciando-se tratamento multidisciplinar com neuropediatra, fisioterapeuta, psicólogo, nutricionista e fonoaudiólogo, além do tratamento medicamentoso com baclofeno e fenobarbital. Discussão: através do tratamento estabelecido, a criança obteve ganho motor, controle cervical, melhora da condição respiratória e sem internações hospitalares, caracterizando uma boa evolução associada particularmente à intervenção fisioterapêutica que teve enfoque na prevenção e minimização de alterações respiratórias frequentemente associadas à morbidades e mortalidade nestes casos. Os resultados obtidos apontam o papel fundamental da intervenção multidisciplinar para o enfrentamento desta condição.

Manejo médico de la distonía / Medical management of dystonia

RESUMEN Para el manejo médico de la distonía se han utilizado tradicionalmente varios fármacos encaminados a disminuir esta condición y a mejorar la calidad de vida. Las terapias orales solas o combinadas proporcionan control parcial de los síntomas y en la mayoría de los casos hay que recurrir a terapias invasivas.

SUMMARY During the last years, several drugs has been tried in order to try to diminish the impact of this condition and improve the quality of life of patients who suffer from dystonia. Oral therapy alone or in combination, generates only partial symptom relief and most of the cases end up requiring other more invasive therapies.

Intoxicaciones agudas por baclofeno consultadas al Centro Nacional de Toxicología en cinco años / Acute intoxications by baclofen consulted to Toxicology National Center in five years

Introducción: el baclofeno se indica como relajante muscular para el alivio de espasticidad grave y ejerce sus efectos como agonista selectivo del receptor GABA-B. Objetivo: caracterizar las intoxicaciones por baclofeno según reportes al Servicio de Información de Urgencia del Cenatox entre 2011 y 2015. Métodos: se realizó un estudio observacional retrospectivo con un universo de 16 notificaciones, en las que se estudiaron: el centro de salud que asistió al paciente, provincia de procedencia por año de estudio, grupo de edad, sexo, circunstancias del evento, manifestaciones clínicas y severidad de la intoxicación. Resultados: el año 2014 aportó la mayor cantidad de reportes y los niños las mayores frecuencias absolutas, no hubo diferencias en relación al sexo, aunque entre los hombres predominó la causa accidental y entre las féminas las intencionales suicidas. Todas las notificaciones procedieron de atención secundaria, aunque cinco de los pacientes habían sido previamente asistidos en áreas de salud. Todos los afectados presentaron manifestaciones neurológicas, la mayoría fueron reportados de grave y la mitad de los casos presentaron alteraciones cardiorrespiratorias con inestabilidad hemodinámica que llevó a la asistencia ventilatoria. La recuperación fue completa en todos los pacientes y no se reportaron fallecidos por esta causa durante el período de estudio. Conclusiones: la sobredosis de baclofeno es más común en niños y cursa con manifestaciones de neurotoxicidad e inestabilidad hemodinámica(AU)

Introduction: Baclofen is indicated as a muscle relaxant for the relief of severe spasticity and exerts its effects as a selective agonist of the GABA-B receptor. Objective: To characterize baclofen poisonings according to reports to the Cenatox emergency information service between 2011 and 2015. Methods: A retrospective observational study with a universe of 16 notifications, in which the health center that attended the patient and province of origin was studied by year of study, age group, gender, circumstances, clinical manifestations and severity of intoxication. Results: The bigger number of reports and the highest absolute frequencies occurred in the year 2014, there were no differences with regard to sex, although among the men, the accidental cause was predominant, and among women the suicides attemps were predominant. All reports came from secondary care, although five of the patients had previously been assisted in health care areas; all affected had neurological manifestations, most were reported as severe and half of the cases presented cardiorespiratory alterations with hemodynamic instability leading to ventilatory assistance. Recovery was complete in all patients and no deaths were reported for this cause during the study period. Conclusions: Baclofen overdose was more common in children and was characterized by neurotoxicity and hemodynamic instability(AU)

Bomba intratecal de baclofeno, ¿una intervención terapéutica útil y segura en pacientes con espasticidad? Presentación de casos / Intrathecal baclofen pump, useful and safe therapeutic intervention in spasticity? Report of four cases / Bomba intratecal de baclofeno, uma intervenção terapêutica útil e segura em doentes com espasti-cidade? Apresentação de casos

La espasticidad puede causar inmovilidad, postración, dolor crónico, úlceras, infecciones, trombosis y neumonías; los objetivos del tratamiento son controlar el dolor, mejorar la movilidad y la calidad de vida y reincorporar al paciente a sus actividades cotidianas por medio de medicamentos antiespásticos orales; sin embargo, los pacientes con espasticidad severa pueden requerir altas dosis orales de estos medicamentos y presentar efectos adversos, por lo que se ha planteado el uso del baclofeno por vía intratecal; en Colombia no se ha usado ampliamente esta intervención y no existen protocolos sobre las indicaciones para llevarla a cabo. El objetivo de esta serie de casos es presentar la experiencia de la Fundación Cardiovascular de Colombia en el tratamiento con bombas intratecales de baclofeno de cuatro pacientes con espasticidad severa, que no habían evolucionado favorablemente con antiespásticos orales, incluyendo altas dosis de baclofeno. Tres de ellos presentaron mejoría importante del dolor, la espasticidad y la calidad de vida, mientras que el otro cursó con síndrome de tolerancia a este medicamento. La bomba intratecal de baclofeno es una intervención útil y segura para pacientes con espasticidad severa que presentan mala respuesta al tratamiento oral o efectos adversos del mismo.

Spasticity may cause immobility, prostration, chronic pain, bedsores, infections, thrombosis and pneumonia; the purposes of its treatment are to control pain, improve mobility and quality of life, and reincorporate the patient to its daily activities by means of oral anti-spastic drugs; however, patients suffering from severe spasticity may require high oral doses of these medications, which may lead to adverse effects. In such cases, intrathecal baclofen has been proposed as a solution. This procedure has not been widely used in Colombia, so that protocols to perform it have not been established. We report the results obtained with the intrathecal administration of baclofen in four severely spastic patients, who had not previously responded to oral anti-spastic drugs, including high doses of baclofen. Pain, spasticity and quality of life significantly improved in three of them. The remaining one presented tolerance to the medication. Intrathecal baclofen pump is a useful and safe procedure for patients with severe spasticity and poorresponse to oral treatment.

A espasticidade pode causar imobilidade, prostração, dor crônico, úlceras, infeções, trombose e pneumonias; os objetivos do tratamento são controlar ador, melhorar a mobilidade e a qualidade de vida e reincorporar ao doente a suas atividades cotidianas por meio de medicamentos anti-espásticos orais; embora, os pacientes com espasticidade severa podem requerer altas doses orais destes medicamentos eapresentar efeitos adversos, pelo que se há planteado o uso do baclofeno por via intratecal; na Colômbia não se há usado amplamente esta intervenção e não existem protocolos sobre as indicações para levá-la a cabo. O objetivo desta série de casos é apresentar a experiência da Fundação Cardiovascular de Colômbia no tratamento com bombas intratecais de baclofeno de quatro doentes com espasticidade severa, que não haviam evolucionado favoravelmente com anti-espásticos orais, incluindo altas dose de baclofeno. Três deles apresentaram melhoria importante da dor, a espasticidade e a qualidade de vida, enquanto que o outro cursou com síndrome de tolerância a este medicamento. a bomba intratecal de baclofeno é uma intervenção útil e segura para doentes com espasticidade severa que apresentam má resposta aotratamento oral ou efeitos adversos do mesmo.

Participação de receptores GABA B na modulação do consumo etílico em ratos Wistar / Involvement of GABA B receptor on ethylic consumption modulation in Wistar rats

Introdução: o baclofeno, uma droga agonista seletivo de GABA B, tem sido apontado como uma nova opção de tratamento do etilismo. Neste estudo avaliou-se o efeito do baclofeno no consumo etílico em ratos Wistar. Materiais e Métodos: o experimento ocorreu em quatro fases: exposição, abstinência, reexposição e tratamento. Os animais foram alocados em grupos: 1, 2, 3 e 4 (n=5 por grupo), expostos à água pura, solução hidroalcoólica (SHA) 5% e SHA 10%; grupo 5 (subdividido em A, B e C N =5 por subgrupo) e grupo 6 (n=5), ambos expostos a apenas água pura. A administração de baclofeno via intraperitoneal destinou aos grupos 1, 2, 3 e 5 em diferentes doses. Nos demais grupos, administrou-se placebo. Aferiu-se o consumo das soluções em todas as fases, para fins comparativos. Resultados: o baclofeno, na dose de 1mg/Kg, reduziu o consumo de SHA 10% no grupo 1, que apresentou maior consumo etílico durante o experimento. Os demais grupos apresentaram menor consumo das SHA ofertadas, sem redução da ingesta etílica após administração da droga nas doses de 2 e 3mg/Kg. Conclusão: baclofeno reduziu etilismo apenas em animais com maior consumo etílico prévio à sua administração. O peso dos animais não foi fator determinante na resposta à droga. A dose efetiva no tratamento dos efeitos da privação alcoólica foi a de menor concentração (1mg/kg).

Introduction: Baclofen, a GABA B agonist, has been pointed as a new drug on the alcohol consumption treatment. This study has evaluated baclofen ́s effect on ethanol consumption in Wistar rats. Materials and Methods: four phases protocol: exposure, abstinence, re-exposure and treatment. Animals were allocated into groups: 1, 2, 3 and 4 (n=5 per group), exposed to pure water, 5% ethanol solution and 10% ethanol solution. Group 5 (subdivided into A, B and C, n=5 by subgroup) and group 6 (n=5), exposed to pure water. Baclofen intraperitoneal administration was destined to groups 1, 2, 3 and 5 (A, B and C) in different doses. The remaining groups received saline solution as control. Solutions consumption was assessed in all phases for comparative purposes. Results: Baclofen at 1mg/Kg reduced the 10% (vv) water-alcohol consumption in animals from Group 1, which also presented greater ethanol consumption during the experiment. The other groups showed a lower water - alcohol consumption and did not show an ethanol intake reduction after the drug administration in both 2 and 3mg/Kg doses. Conclusion: Baclofen only reduces alcoholism in animals with higher ethanol consumption. Animals weight is not a determining factor in ethanol consumption or in baclofen response. The effective baclofen dose in treating the deprivation alcohol effects was observed in the lowest concentration, corresponding to 1mg/Kg dose.

Infraestructura, ingreso y desnutrición infantil en México / Child malnutrition, infrastructure and income in Mexico

Objetivo. Explicar la variación de la desnutrición infantil (DI), entendida como baja talla para la edad (0 a 5 años) entre 1999 y 2006. Material y métodos. Se emplearon estimaciones estatales de DI y diversos indicadores que reflejan las probables causas subyacentes del fenómeno como la pobreza, el producto per cápita estatal, la educación de las mujeres y los accesos a infraestructura de salud y de drenaje. Para el análisis de datos se utilizaron los métodos de regresión con datos panel de efectos fijos y aleatorios. Resultados. Se encontró que la carencia de salud y drenaje, así como la pobreza, empeoran la DI, mientras que la educación de las mujeres la disminuye. Conclusiones. El estudio muestra que las variables de infraestructura explican en buena parte la variación reciente de la DI entre estados, y que el crecimiento económico no es una condición suficiente para reducir la DI.

Objective. Explain the variation in child malnutrition (CM), understood as low height for age (0 to 5 years old) for the period 1999-2006. Materials and methods. State estimations of child malnutrition and several indicators of subjacent probable causes of CM were employed, such as poverty indices, state product per capita, women scholar attainment and access to health and the sewage system. Panel data regression analysis with fixed and random effects were used to analyze the data. Results. The results indicate that the lack to access to health and sewage systems and poverty worsen CM, whereas women education helps to diminish CM. Conclusion. The study shows that infrastructure variables explain a significant part of the recent variation in DI across Mexican states, and that economic growth is not a sufficient condition to diminish DI.

Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats / Mecanismos Neurais e Retardo do Esvaziamento Gástrico de Liquido Induzido no Infarto Agudo do Miocárdio em Ratos

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN. .

Fundamento: Distúrbios da motilidade do intestino proximal no infarto agudo do miocárdio podem desencadear sintomas digestivos como náuseas e vômitos. O infarto do miocárdio ocasiona retardo do esvaziamento gástrico (EG) de líquido em ratos. Objetivo: Investigar se existe a influência do nervo vago (VGX), adrenoreceptores α-1, receptores GABAB do sistema nervoso central e participação do núcleo paraventricular (NPV) do hipotálamo no esvaziamento gástrico (EG) e complacência gástrica (CG) em ratos infartados. Métodos: Ratos Wistar (n = 8-15) foram divididos em: grupo infarto (INF), sham (SH) e subdivididos. O infarto foi realizado por ligadura da artéria coronária descendente anterior. A complacência gástrica foi estimada com curvas pressão-volume. Realizada vagotomia por secção dos ramos dorsal e ventral. Para verificar a ação dos receptores GABAB foi injetado baclofeno por via intra ventrículo-cerebral. Simpatectomia química foi realizada com prazosina intravenosa (iv), e na lesão do núcleo paraventricular do hipotálamo foi utilizada corrente elétrica de 1mA/10s, com esvaziamento gástrico determinado por medição da retenção gástrica (% RG) de uma refeição salina. Resultados: Não houve diferença significativa na CG. A vagotomia (VGX) reduziu significativamente a %RG; no grupo INF, o tratamento intra ventrículo-cerebral (ivc) com baclofeno reduziu significativamente a % RG; não houve conclusivamente envolvimento dos receptores GABAB em retardar o EG; o tratamento intravenoso com prazosina reduziu significativamente a %RG no grupo INF. A lesão do NPV aboliu o efeito do infarto do miocárdio no EG. Conclusão: O nervo vago, receptores α-adrenérgicos e núcleo paraventricular estão envolvidos no retardo do esvaziamento gástrico no infarto agudo do miocárdio em ratos. .

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): typical clinical and neuroimaging features in a Brazilian family / Ataxia espástica autossômica recessiva de Charlevoix-Saguenay (ARSACS): aspectos clínicos e de neuroimagem típicos em uma família brasileira

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder characterized by late-infantile onset spastic ataxia and other neurological features. ARSACS has a high prevalence in northeastern Quebec, Canada. Several ARSACS cases have been reported outside Canada in recent decades. This is the first report of typical clinical and neuroimaging features in a Brazilian family with probable diagnosis of ARSACS.

A ataxia espástica autossômica recessiva de Charlevoix-Saguenay (ARSACS) é doença degenerativa do sistema nervoso, caracterizada por ataxia associada a espasticidade, entre outras manifestações neurológicas, de início na infância. A doença tem alta prevalência na região de Quebec, no Canadá. Muitos relatos de ARSACS têm sido descritos fora do Canadá nas últimas décadas. Nesse artigo, relatamos a primeira descrição dos aspectos clínicos e de neuroimagem típicos em uma família brasileira com provável diagnóstico de ARSACS.

Effect of baclofen on liquid and solid gastric emptying in rats / Efeito do baclofen no esvaziamento gástrico de líquido e de sólidos em rato

CONTEXT: Gamma-aminobutyric acid (GABA) is a potent inhibitory neurotransmitter. There is evidence that GABA B receptors located in the dorsal complex and in afferent fibers of the vagus nerve participate in the control of gastrointestinal motility. OBJECTIVE: To assess the intracerebroventricularly (ICV) and intravenously (IV) effect of baclofen, a GABA B receptor agonist, on liquid and solid gastric emptying in rats. METHODS: Adult male Wistar rats weighing 250-300 g (n = 6-8 animals) were used. Gastric emptying of liquid test meals labeled with phenol red was evaluated by the determination of percent gastric retention ( percentGR) 10 and 15 min after orogastric administration of saline and 10 percent glucose meals, respectively. Baclofen was injected ICV (1 and 2 µg/animal) through a tube implanted into the lateral ventricle of the brain and was injected IV (1 and 2 mg/kg) into a tail vein. The gastric emptying of liquid was determined 10 or 30 min after ICV and IV baclofen administration, respectively. The gastric emptying of the solid meal was assessed by the determination of percent gastric retention 2 h after the beginning of the ingestion of the habitual ratio by the animal, consumed over a period of 30 min. Baclofen was administered ICV (1 and 2 µg/animal) or IV (1 and 2 mg/kg) immediately after the end of the ingestion of the solid meal. The control groups received vehicle (sterile saline solution) ICV or IV. RESULTS: The group of animals receiving baclofen ICV (2 mg/animal) presented a significantly lower (P<0.05, Tukey test) percentGR (mean ± SEM) of the saline (18.1 ± 2.5 percent) compared to control (33.2 ± 2.2 percent). In the group receiving the drug IV, the gastric retention of the same test meal did not differ from control. ICV and IV administration of baclofen had no effect on the gastric emptying of the 10 percent glucose solution compared to control. ICV administration of 1 or 2 mg baclofen/animal significantly increased the gastric retention of the solid test meal (57.9 ± 6.5 percent and 66.6 ± 6.3 percent, respectively) compared to control (35.1 ± 4.4 percent). The same phenomenon was observed only with the IV dose of 2 mg/kg (71.9 ± 2.6 percent) compared to control (52.7 ± 2.8 percent). CONCLUSION: Baclofen administered: 1. ICV (2 µg/animal), but not IV, increased gastric emptying of a non-caloric isotonic liquid test meal (saline); 2. when administered ICV or IV, it had no effect of gastric emptying of a 10 percent glucose solution; 3) when administered ICV (1 and 2 mg/animal) and IV (2 mg/kg) it delayed the gastric emptying of the solid meal.

CONTEXTO: O ácido gama-aminobutírico (GABA) é um potente neurotransmissor inibitório. Há evidências que receptores GABA>B localizados no complexo dorsal do vago e em fibras aferentes do nervo vago participam no controle da motricidade gastrointestinal. OBJETIVO: Avaliar o efeito intracerebroventricular (ICV) e intravenoso (IV) do baclofen, um agonista para receptores GABA B, sobre o esvaziamento gástrico de líquidos e de sólidos em ratos. MÉTODOS: Foram utilizados ratos adultos Wistar, machos, de 250-300 g (n = 6-8 animais). O esvaziamento gástrico das refeições de prova líquidas, marcadas com fenol vermelho, foi avaliado através da determinação da por cento de retenção gástrica, 10 e 15 min após administração orogástrica das refeições salina e de glicose a 10 por cento, respectivamente. As injeções ICV de baclofen (1 e 2 µg/animal) foram feitas através de uma sonda implantada no ventrículo lateral do cérebro e as injeções IV de baclofen (1 e 2 mg/kg) numa veia da cauda. O esvaziamento gástrico das refeições de prova líquidas foi determinado 10 ou 30 min após a administração de baclofen ICV ou IV, respectivamente. O esvaziamento gástrico da refeição sólida foi avaliado através da determinação da por cento de retenção gástrica 2 h após o início da ingestão da ração habitual do animal, ingerida durante 30 min. As administrações de baclofen ICV (1 e 2 µg/animal) e IV (1 e 2 mg/kg) foram feitas imediatamente após o término da ingestão da refeição sólida. Os grupos controles receberam ICV ou IV veículo (solução salina estéril). RESULTADOS: O grupo de animais que recebeu baclofen 2 mg/animal ICV apresentou retenção gástrica (média ± SEM) de salina (18.1 ± 2.5 por cento) significantemente menor (P<0.05, teste de Tukey) em relação ao grupo controle (33.2 ± 2.2 por cento). No grupo com administração IV da droga, a retenção gástrica da mesma refeição de prova não diferiu do seu controle. As administrações ICV e IV de baclofen não tiveram qualquer efeito no esvaziamento gástrico da solução de glicose a 10 por cento, em relação aos seus controles. A administração ICV de 1 ou 2 µg/animal de baclofen aumentou significativamente as retenções gástricas da refeição de prova sólida (57.9 ± 6.5 por cento e 66.6 ± 6.3 por cento, respectivamente) em relação ao grupo controle (35.1 ± 4.4 por cento). O mesmo fenômeno somente foi observado com a dose IV de 2 mg/kg (71.9 ± 2.6 por cento) em relação ao grupo controle (52.7 ± 2.8 por cento). CONCLUSÃO: O baclofen administrado: 1. ICV (2 µg/animal), mas não IV, aumentou o esvaziamento gástrico de uma refeição de prova líquida isotônica não-calórica (salina); 2. ICV ou IV, não teve efeito sobre o esvaziamento da solução de glicose a 10 por cento; 3) ICV (1 e 2 µg/animal) e IV (2 mg/kg) retardou o esvaziamento gástrico da refeição sólida.

Actividad del Flumazenil sobre el efecto depresor del Baclofén / Flumazenil acctivity on the depressing effect induced by Baclofen

Es un estudio experimental tipo ensayo terapéutico realizado en 200 ratones machos cepa NMRI, de 8 a 12 semanas de edad y peso de 31,7 gr pertenecientes al bioterio de la Uni versidad de Los Andes, con la finalidad de determinar si el Flumazenil es un antagonista competitivo o no competitivo, y su actividad sobre el efecto depresor inducido por el Baclofén mediante la evaluación de la actividad locomotora y la prueba de la barra horizontal. Previamente se estableció la dosis letal del Baclofén en 110 ratones, obteniendo una DL50 de 40,88 mg/kg para este estudio. Los resultados indican que el Flumazenil elevó la dosis letal a 47,92 mg/kg. En la prueba de la barra horizontal, prolongó el tiempo de caída de los ratones. Sobre la actividad locomotora, la administración de Baclofén produjo una reducción durante la 1ª hora (22,71%), y elevación durante la 2ª y 3ª ho ras (45,27% y 30,62% respectivamente). En el grupo trata do con Flumazenil más Baclofén se observó una reducción de la actividad locomotora en la tres horas de observación (67,47%, 60,12% y 45,85%) Se comprobó que no existe desvío de paralelismo entre las dos rectas de la curva gráfica de dosis-respuesta. Conclusión: No se conoce un antídoto efectivo para contrarrestar la depresión del SNC inducida por el Baclofén. El Flumazenil es un antagonista competitivo que actúa a nivel de los receptores gammaaminobutíricos. Se demostró en este estudio que el Flumazenil retrasó la mortalidad inducida por el Baclofén.

It is a comparative study and experimental field conducted in 100 male mice NMRI class, 8 to 12 weeks and weighing 31.7 grams of bioterio de la Universidad de Los Andes, with the aim of establishing the locomotor activity and test bar horizontal Flumazenil on the depressing effect induced by Baclofen. Before establishing the dose lethality of baclofen in 40.88 mg / kg for this study. The results indicate that Flumazenil rose 47.92 a lethal dose mg / kg. In proof of the horizontal bar, prolonged the time to drop in mice. In the group treated with Flumazenil more Baclofen was observed a reduction in activity locomotive to three hours, while Baclofen produced declined during the first hour, 1, and elevators during the 2 nd and 3 rd hour. It was found that there is no parallelism between the two lines of the dose-response curve. Conclusion: There is no known antidote to counteract the effects of the central nervous system depression induced by Baclofen. The Flumazenil is an antagonist benzodiazepines, which operates a level of receptors ganmaaminobutíricos, was demonstrated in this study decrease in mortality induced by Baclofen.

Effect of antipyrine on the gastric emptying of liquid in rats

Antipyrine (At) and dipyrone (Dp) delay gastric emptying (GE) in rats. The objective of the present study was to assess the effects of intravenous (iv) and intracerebroventricular (icv) administration of At and Dp on the GE of liquid by rats. GE was assessed in male Wistar rats (5-10 in each group) 10 min after the icv or iv drug injection by measuring percent gastric retention ( percentGR) of a saline test meal labeled with phenol red 10 min after administration by gavage. The At iv group was significantly higher (64.4 ± 2.6 percent) compared to control (33.4 ± 1.5 percent) but did not differ from the Dp group (54.3 ± 3.8 percent). After icv administration of At, percentGR (34.2 ± 2 percent) did not differ from control (32.6 ± 1.9 percent), but was significantly higher after Dp (54.5 ± 2.3 percent). Subdiaphragmatic vagotomy significantly reduced percentGR in the At group (30.2 ± 0.7 percent) compared to the sham group, but was significantly higher than in the controls (23.0 ± 0.5 percent). In the animals treated with At iv, baclofen significantly reduced percentGR (28.3 ± 2.4 percent) compared to vehicle-treated animals (55.2 ± 3.2 percent). The same occurred in the animals treated iv with vehicle and icv with baclofen. Although vagotomy and baclofen reduced percentGR per se, the reduction was twice more marked in the animals treated with At. The results suggest that At administered iv, but not icv, delays GE of liquid in rats with the participation, at least in part, of the vagus nerve and that this phenomenon is blocked by the activation of GABA B receptors in the central nervous system.

The bradycardic and hypotensive responses to serotonin are reduced by activation of GABA A receptors in the nucleus tractus solitarius of awake rats

We investigated the effects of bilateral injections of the GABA receptor agonists muscimol (GABA A) and baclofen (GABA B) into the nucleus tractus solitarius (NTS) on the bradycardia and hypotension induced by iv serotonin injections (5-HT, 2 æg/rat) in awake male Holtzman rats. 5-HT was injected in rats with stainless steel cannulas implanted bilaterally in the NTS, before and 5, 15, and 60 min after bilateral injections of muscimol or baclofen into the NTS. The responses to 5-HT were tested before and after the injection of atropine methyl bromide. Muscimol (50 pmol/50 nl, N = 8) into the NTS increased basal mean arterial pressure (MAP) from 115 ± 4 to 144 ± 6 mmHg, did not change basal heart rate (HR) and reduced the bradycardia (-40 ± 14 and -73 ± 26 bpm at 5 and 15 min, respectively, vs -180 ± 20 bpm for the control) and hypotension (-11 ± 4 and -14 ± 4 mmHg, vs -40 ± 9 mmHg for the control) elicited by 5-HT. Baclofen (12.5 pmol/50 nl, N = 7) into the NTS also increased basal MAP, but did not change basal HR, bradycardia or hypotension in response to 5-HT injections. Atropine methyl bromide (1 mg/kg body weight) injected iv reduced the bradycardic and hypotensive responses to 5-HT injections. The stimulation of GABA A receptors in the NTS of awake rats elicits a significant increase in basal MAP and decreases the cardiac Bezold-Jarisch reflex responses to iv 5-HT injections.

Effect of the GABA B agonist baclofen on dipyrone-induced delayed gastric emptying in rats

Dipyrone administered intravenously (iv) or intracerebroventricularly (icv) delays gastric emptying (GE) in rats. Gamma-aminobutyric acid (GABA) is the most potent inhibitory neurotransmitter of the central nervous system. The objective of the present study was to determine the effect of icv baclofen, a GABA B receptor agonist, on delayed GE induced by dipyrone. Adult male Wistar rats received a saline test meal containing phenol red as a marker. GE was indirectly evaluated by determining the percent of gastric retention ( percentGR) of the meal 10 min after orogastric administration. In the first experiment, the animals were injected iv with vehicle (Civ) or 80 mg/kg (240 æmol/kg) dipyrone (Dp iv), followed by icv injection of 10 æl vehicle (bac0), or 0.5 (bac0.5), 1 (bac1) or 2 æg (bac2) baclofen. In the second experiment, the animals were injected icv with 5 æl vehicle (Cicv) or an equal volume of a solution containing 4 æmol (1333.2 æg) dipyrone (Dp icv), followed by 5 æl vehicle (bac0) or 1 æg baclofen (bac1). GE was determined 10 min after icv injection. There was no significant difference between control animals from one experiment to another concerning GR values. Baclofen at the doses of 1 and 2 æg significantly reduced mean percentGR induced by iv dipyrone (Dp iv bac1 = 35.9 percent and Dp iv bac2 = 26.9 percent vs Dp iv bac0 = 51.8 percent). Similarly, baclofen significantly reduced the effect of dipyrone injected icv (mean percentGR: Dp icv bac1 = 30.4 percent vs Dp icv bac0 = 54.2 percent). The present results suggest that dipyrone induces delayed GE through a route in the central nervous system that is blocked by the activation of GABA B receptors.

Espasticidad y baclofen intratecal complicaciones y riesgos derivados del sistema / Spasticity and banclofen intrathecal complications and risks derivados of the system

El Presente trabajo refleja un estudio experimental del riesgo de Baclofen mediante infusión intratecal. Se llevó a cabo en 23 pacientes en la clínica de la concepción (Fundación Giménez Díaz) Madrid. La evaluación del sistema de infusión se realizó a cada rellenado del dispositivo y se valoró al mismo tiempo la dosis eficaz, además se hizo un seguimiento de las posibles complicaciones y riesos derivados del sistema a lo largo de 52 meses. Tres de los pacientes han tenido meningitis en la fase de prueba. Alucinaciones, agitación e inquietud en 3 como consecuencia de una deprivación brusca del fármaco. Hipotonia, somnolencia, disfagia en 2 pacientes por sobredosis, en doce se produjo dehiscencia de la incisión. Un Paciente, desconexión del catéter y en otro la oclusión. Una bomba fue bloqueada al pasar el enfermo por un detector de metales en un comercio. Palabras claves: Baclofen, Baclofen intratecal, Espasticidad, Bombas de infusión, Riesgos de Baclofen.

Baclofen intratecal no tratamento da espasticidade de origem medular / Intrathecal baclofen for the treatment of spinal spasticity

O objetivo deste trabalho foi avaliar a longo termo aspectosclínicos e técnicos do uso do baclofen intratecal por bomba deinfusão em pacientes portadores de espasticidade crônica deorigem medular.São analisados 122 pacientes portadores de espasticidademedular, operados entre 1989 e 2001, sendo 74 homens e 48mulheres, com média de idade de 45 anos, apresentando tempo deseguimento médio de cinco anos. Quanto à origem da lesãomedular, em 46 pacientes foi pós-traumática, em 52, por esclerosemúltipla e 24 pacientes tiveram outras causas (lesão pósoperatória,isquêmica ou pós-radioterapia).Todos os pacientes tiveram redução da hipertonia muscularcom diminuição dos espasmos dolorosos. Em 19 pacientes(15,6), o tratamento proposto resultou em melhora funcionaldo paciente. Nos outros 103 casos (84,4), a diminuição daespasticidade promoveu melhora objetiva no manejo do paciente,nos cuidados de enfermagem, de higiene pessoal e de transporte.De acordo com a escala de Ashworth, a pontuação média caiu de 3,0 para 1,4, enquanto na escala de freqüência de espasmo aqueda foi de 2,5 para 0,7. A dose média inicial de baclofen foi250 μg/dia, chegando progressivamente a 358 μg/dia, com grandevariabilidade individual. Complicações técnicas relacionadas aomaterial de implantação ocorreram em 36 casos (29,5) ecomplicações clínicas, relacionadas ao baclofen, foram observadasem 17 casos (13,9). Não houve óbitos relacionados aotratamento nesta série.O baclofen intratecal por bomba de infusão programável éuma modalidade terapêutica eficaz no tratamento da espasticidadecrônica de origem medular. O tratamento multidisciplinaré fundamental tanto na seleção como no acompanhamento dospacientes.