RESUMO
Resumen Introducción: La vinpocetina de liberación prolongada ha demostrado ser efectiva en el control de crisis de inicio focal en pacientes epilépticos con una baja frecuencia de eventos adversos. Se realizó un estudio clínico para evaluar la eficacia y tolerabilidad de la vinpocetina como tratamiento adyuvante en pacientes con este padecimiento. Métodos: Se realizó un estudio clínico, doble ciego, de grupos paralelos. Se reclutaron 87 pacientes con diagnóstico de epilepsia focal tratados con uno a tres fármacos antiepilépticos. Los pacientes se aleatorizaron para ser tratados con vinpocetina (n = 41) o placebo (n = 46) de manera adyuvante a su tratamiento, e ingresaron a la fase basal (4 semanas), a la fase de titulación (4 semanas) y a la fase de evaluación (8 semanas) conservando estables las dosis de la vinpocetina y de los fármacos antiepilépticos. Resultados: La vinpocetina fue más efectiva que el placebo en la reducción de las crisis al finalizar la fase de evaluación (p < 0.0001). El 69% de los pacientes tratados con vinpocetina presentaron una reducción mayor al 50% en las crisis en comparación con el 13% de los pacientes tratados con placebo. No se presentaron diferencias significativas en cuanto a la presencia de efectos adversos en los pacientes tratados con vinpocetina comparados con los tratados con placebo. Los eventos adversos más frecuentes observados con vinpocetina fueron cefalea (7.9%) y diplopía (5.2%). Conclusiones: Como tratamiento adyuvante, la vinpocetina (2 mg/kg/día) redujo eficazmente la frecuencia de crisis epilépticas y demostró ser bien tolerada. Presenta un amplio perfil de seguridad y eventos adversos conocidos, que son transitorios y sin secuelas.
Abstract Background: Extended-release vinpocetine is effective to control focal onset epileptic seizures with a low rate of adverse events. A clinical study was performed to evaluate the efficacy and tolerability of vinpocetine as an adjuvant treatment in patients with this condition. Methods: A double-blind clinical study of parallel groups was conducted, in which 87 patients with a diagnosis of focal epilepsy treated with one to three antiepileptic drugs were recruited. Patients were randomized to receive vinpocetine (n = 41) or placebo (n = 46) adjuvant to their treatment. Patients entered the baseline phase (4 weeks), the titration phase (4 weeks) and the evaluation phase (8 weeks), maintaining stable doses of vinpocetine and their respective antiepileptic drug treatment. Results: Vinpocetine was more effective than placebo in reducing seizures at the end of the evaluation phase (p < 0.0001). Sixty-nine percent of the vinpocetine-treated patients had a 50% reduction in seizures compared to 13% of placebo-treated patients. No significant differences in the presence of adverse effects in patients treated with vinpocetine compared to those treated with placebo were observed. The most frequent adverse events observed with vinpocetine were headache (7.9%) and diplopia (5.2%). Conclusions: As an adjuvant treatment, vinpocetine (2 mg/kg/day) effectively reduced the frequency of epileptic seizures and proved to be well tolerated. Vinpocetine has a wide safety profile and well-known adverse events, which are transient and with no sequelae.
Assuntos
Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Alcaloides de Vinca/administração & dosagem , Epilepsias Parciais/tratamento farmacológico , Anticonvulsivantes/administração & dosagem , Alcaloides de Vinca/efeitos adversos , Método Duplo-Cego , Estudos Longitudinais , Resultado do Tratamento , Preparações de Ação Retardada , Anticonvulsivantes/efeitos adversosRESUMO
Background: Extended-release vinpocetine is effective to control focal onset epileptic seizures with a low rate of adverse events. A clinical study was performed to evaluate the efficacy and tolerability of vinpocetine as an adjuvant treatment in patients with this condition. Methods: A double-blind clinical study of parallel groups was conducted, in which 87 patients with a diagnosis of focal epilepsy treated with one to three antiepileptic drugs were recruited. Patients were randomized to receive vinpocetine (n = 41) or placebo (n = 46) adjuvant to their treatment. Patients entered the baseline phase (4 weeks), the titration phase (4 weeks) and the evaluation phase (8 weeks), maintaining stable doses of vinpocetine and their respective antiepileptic drug treatment. Results: Vinpocetine was more effective than placebo in reducing seizures at the end of the evaluation phase (p < 0.0001). Sixty-nine percent of the vinpocetine-treated patients had a 50% reduction in seizures compared to 13% of placebo-treated patients. No significant differences in the presence of adverse effects in patients treated with vinpocetine compared to those treated with placebo were observed. The most frequent adverse events observed with vinpocetine were headache (7.9%) and diplopia (5.2%). Conclusions: As an adjuvant treatment, vinpocetine (2 mg/kg/day) effectively reduced the frequency of epileptic seizures and proved to be well tolerated. Vinpocetine has a wide safety profile and well-known adverse events, which are transient and with no sequelae.
Introducción: La vinpocetina de liberación prolongada ha demostrado ser efectiva en el control de crisis de inicio focal en pacientes epilépticos con una baja frecuencia de eventos adversos. Se realizó un estudio clínico para evaluar la eficacia y tolerabilidad de la vinpocetina como tratamiento adyuvante en pacientes con este padecimiento. Métodos: Se realizó un estudio clínico, doble ciego, de grupos paralelos. Se reclutaron 87 pacientes con diagnóstico de epilepsia focal tratados con uno a tres fármacos antiepilépticos. Los pacientes se aleatorizaron para ser tratados con vinpocetina (n = 41) o placebo (n = 46) de manera adyuvante a su tratamiento, e ingresaron a la fase basal (4 semanas), a la fase de titulación (4 semanas) y a la fase de evaluación (8 semanas) conservando estables las dosis de la vinpocetina y de los fármacos antiepilépticos. Resultados: La vinpocetina fue más efectiva que el placebo en la reducción de las crisis al finalizar la fase de evaluación (p < 0.0001). El 69% de los pacientes tratados con vinpocetina presentaron una reducción mayor al 50% en las crisis en comparación con el 13% de los pacientes tratados con placebo. No se presentaron diferencias significativas en cuanto a la presencia de efectos adversos en los pacientes tratados con vinpocetina comparados con los tratados con placebo. Los eventos adversos más frecuentes observados con vinpocetina fueron cefalea (7.9%) y diplopía (5.2%). Conclusiones: Como tratamiento adyuvante, la vinpocetina (2 mg/kg/día) redujo eficazmente la frecuencia de crisis epilépticas y demostró ser bien tolerada. Presenta un amplio perfil de seguridad y eventos adversos conocidos, que son transitorios y sin secuelas.
Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsias Parciais/tratamento farmacológico , Alcaloides de Vinca/administração & dosagem , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Criança , Preparações de Ação Retardada , Método Duplo-Cego , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Alcaloides de Vinca/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Maternal alcohol use during pregnancy causes a continuum of long-lasting disabilities in the offspring, commonly referred to as fetal alcohol spectrum disorder (FASD). Attention-deficit/hyperactivity disorder (ADHD) is possibly the most common behavioral problem in children with FASD and devising strategies that ameliorate this condition has great clinical relevance. Studies in rodent models of ADHD and FASD suggest that impairments in the cAMP signaling cascade contribute to the hyperactivity phenotype. In this work, we investigated whether the cAMP levels are affected in a long-lasting manner by ethanol exposure during the third trimester equivalent period of human gestation and whether the acute administration of the PDE1 inhibitor vinpocetine ameliorates the ethanol-induced hyperactivity. METHODS: From postnatal day (P) 2 to P8, Swiss mice either received ethanol (5g/kg i.p.) or saline every other day. At P30, the animals either received vinpocetine (20mg/kg or 10mg/kg i.p.) or vehicle 4h before being tested in the open field. After the test, frontal cerebral cortices and hippocampi were dissected and collected for assessment of cAMP levels. RESULTS: Early alcohol exposure significantly increased locomotor activity in the open field and reduced cAMP levels in the hippocampus. The acute treatment of ethanol-exposed animals with 20mg/kg of vinpocetine restored both their locomotor activity and cAMP levels to control levels. CONCLUSIONS: These data lend support to the idea that cAMP signaling system contribute to the hyperactivity induced by developmental alcohol exposure and provide evidence for the potential therapeutic use of vinpocetine in FASD.
Assuntos
Consumo de Bebidas Alcoólicas/patologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtornos do Espectro Alcoólico Fetal/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Alcaloides de Vinca/farmacologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Animais , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Depressores do Sistema Nervoso Central/efeitos adversos , Depressores do Sistema Nervoso Central/sangue , Depressores do Sistema Nervoso Central/toxicidade , AMP Cíclico/análise , Modelos Animais de Doenças , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos , Etanol/efeitos adversos , Etanol/sangue , Etanol/toxicidade , Feminino , Humanos , Masculino , Camundongos , Inibidores de Fosfodiesterase/administração & dosagem , Inibidores de Fosfodiesterase/efeitos adversos , Inibidores de Fosfodiesterase/uso terapêutico , Gravidez , Complicações na Gravidez/induzido quimicamente , Método Simples-Cego , Taxa de Sobrevida , Alcaloides de Vinca/administração & dosagem , Alcaloides de Vinca/efeitos adversos , Alcaloides de Vinca/uso terapêutico , Aumento de Peso/efeitos dos fármacosRESUMO
The effects of two classic antiepileptic drugs (carbamazepine and phenytoin), a potential antiepileptic (vinpocetine) and a monoamine-oxidase inhibitor (clorgyline) on the simultaneous changes (detected by HPLC) on Glu, Asp, dopamine and DOPAC inside and outside striatal isolated nerve endings were investigated. Under resting conditions phenytoin, carbamazepine and clorgyline increased dopamine release. Phenytoin and clorgyline increased internal dopamine and decreased DOPAC formation. Carbamazepine decreased internal dopamine and practically did not change DOPAC formation. Glu and Asp release was unchanged. Neurotransmitter release induced by the Na+ channel opener veratridine was reduced by all the antiepileptic drugs tested, except phenytoin which, like clorgyline, facilitated veratridine-induced dopamine release. We conclude that besides the antagonism exerted by carbamazepine, phenytoin and vinpocetine on excitatory neurotransmitters release triggered by Na+ channel activation, that might importantly contribute to their anticonvulsant action, they exert different actions on striatal dopamine distribution, that might explain their different side effect profiles.