Prescription patterns of riluzole in a population of patients with motor neuron disease / Patrón de prescripción de riluzol en una población de pacientes con enfermedad de neurona motora

SUMMARY OBJECTIVE: To determine the prescription pattern of riluzol and the variables associated to its use in a population of patients with motor neuron disease affiliated to the Colombian General Social Security Health System (SGSSS) in 2017. METHOD: Descriptive cross-sectional study. Through a systemized data base of approximately 3,5 million members to the Colombian SGSSS; patients who had been given riluzol uninterruptedly between April 1 and June 30 of 2017, were selected. Sociodemographic, pharmacological variables and comorbidities were analyzed. Defined daily dose (DDD) was estimated for 1.000 inhabitants/day and its costs. RESULTS: There were found 81 patients with motor neuron disease receiving riluzol, with an average age of 60,8+12,6 years. 48.1% were male. The prevalence of motor neuron disease was 29/100.000 individuals. Patients received riluzol in 50 mg tablets and the doses was estimated in 0,016 DDD for 1.000 inhabitants/day 63% were receiving medicines that reflect comorbidity or could interact with riluzol. The total cost of riluzol dispensed in 2017 was USD 85.348 and per prescribed daily dose on average was USD 2,3. CONCLUSIONS: The use of riluzol in patients with motor neuron disease in Colombia was carried by the recommended doses by the WHO and with a direct cost lower than reported in other countries. Studies are recommended in order to determine the effectiveness of riluzol in real-life conditions.

RESUMEN OBJETIVOS: Determinar el patrón de prescripción de riluzol y las variables asociadas a su utilización en una población de pacientes con enfermedad de neurona motora afiliados al Sistema General de Seguridad Social en Salud de Colombia (SGSSS) en 2017. METODOLOGÍA: Estudio descriptivo de corte transversal. Mediante una base de datos sistematizada de aproximadamente 3,5 millones de afiliados al SGSSS de Colombia; se seleccionaron pacientes a quienes se les haya dispensado riluzol de manera ininterrumpida entre 1 abril y 30 junio de 2017. Se analizaron variables socio-demográficas, farmacológicas y las comorbilidades. Se estimaron la dosis diaria definida (DDD) por 1.000 habitantes/día y los costos. RESULTADOS: Se encontraron 81 pacientes con enfermedad de neurona motora recibiendo riluzol, con edad promedio de 60,8+12,6 años. El 48,1% eran hombres. La prevalencia de enfermedad de neurona motora fue 2,29/100.000 personas. Los pacientes recibieron riluzol en tabletas de 50 mg y se estimó la dosis en 0,016 DDD por 1.000 habitantes/día. El 63% recibían medicamentos que reflejan comorbilidad o pudieran tener interacción con riluzol. El costo total del riluzol dispensado en 2017 fue USD 85.348 y por dosis diaria prescrita en promedio fue USD 2,3. CONCLUSIONES: El uso de riluzol en pacientes con enfermedad de neurona motora en Colombia se realizó a las dosis recomendadas por la OMS y con un costo directo menor al reportado en otros países. Se recomienda realizar estudios que permitan determinar la efectividad del riluzol en condiciones de la vida real.

The Effects of Riluzole on Cisplatin-induced Ototoxicity

Abstract Introduction Riluzole (2-amino-6-trifluoromethoxy benzothiazole) is known as a neuroprotective, antioxidant, antiapoptotic agent. It may have beneficial effects on neuronal cell death due to cisplatin-induced ototoxicity. Objective To evaluate the effect of riluzole on cisplatin-induced ototoxicity in guinea pigs. Methods Twenty-four guinea pigs, studied in three groups, underwent auditory brainstem response evaluation using click and 8 kHz tone burst stimuli. Subsequently, 5 mg/kg of cisplatin were administered to all animals for 3 days intraperitoneally (i.p.) to induce ototoxicity. Half an hour prior to cisplatin, groups 1, 2 and 3 received 2 ml of saline i.p., 6 mg/kg of riluzole hydrochloride i.p., and 8 mg/kg of riluzole hydrochloride i.p., respectively, for 3 days. The auditory brainstem responses were repeated 24 hours after the last drug administration. The cochleae were analyzed by transmission electron microscopy (TEM). Results After drug administiration, for 8,000 Hz stimulus, group 1 had significantly higher threshold shifts when compared with groups 2 (p < 0.05) and 3 (p < 0.05), and there was no significant difference in threshold shifts between groups 2 and 3 (p > 0.05). Transmission electron microscopy findings demonstrated the protective effect of riluzole on the hair cells and the stria vascularis, especially in the group treated with 8 mg/kg of riluzole hydrochloride. Conclusion We can say that riluzolemay have a protective effect on cisplatin- induced ototoxicity. However, additional studies are needed to confirm these results and the mechanisms of action of riluzole.

Sobrevida en pacientes con Esclerosis Lateral Amiotrófica / Survival in patients with Amyotrophic Lateral Sclerosis

RESUMEN Introducción: La esclerosis lateral amiotrófica (ELA) es la más frecuente del grupo heterogéneo de las enfermedades de la motoneurona. Objetivo: Caracterizar la sobrevida de los pacientes con diagnóstico de esclerosis lateral amiotrófica partiendo de factores relacionados con su comportamiento clínico en el Instituto Nacional de Neurología y Neurocirugía "Dr. José Rafael Estrada González" de a Habana, Cuba. Material y Métodos: Se realizó una investigación descriptiva y retrospectiva de una serie de 147 casos de pacientes diagnosticados con ELA, por la confirmación clínica, neurofisiológica e imágenes, atendidos en la consulta multidisciplinaria en el periodo de octubre de 2005 a octubre de 2015, de los cuales ya han fallecido 110. Resultados: La mayor frecuencia de la enfermedad por grupos de edades estuvo entre 51 y 60 años. En los primeros 40 meses murió la mayor parte de los pacientes (80). La forma clínica espinal predominó en varones quienes, además, tuvieron mayor sobrevida, la bulbar prevaleció en mujeres. El mayor número de pacientes no tenía factores de riesgo. Entre las comorbilidades destacan la diabetes, hipertensión arterial, enfermedad cerebrovascular isquémica, neoplasias, hepatitis C, traumatismo craneal, asma bronquial y la cardiopatía isquémica, y hubo casos de la enfermedad en una misma familia. Conclusiones: La mayor sobrevida desde el diagnóstico de la enfermedad estuvo en el grupo de 51 a 60 años alcanzando algunos hasta 10 años. El promedio general de sobrevida estuvo entre 2 y 5 años. En los pacientes con comorbilidades, antecedentes familiares y forma bulbar, la sobrevida fue menor. La supervivencia al evaluar la efectividad del tratamiento con Riluzol no fue significativa.

ABSTRACT Introduction: Amyotrophic lateral sclerosis (ALS) is the most frequent disease in the heterogeneous group of disorders with motor neuron diseases. Objective: To characterize the survival of patients diagnosed with amyotrophic lateral sclerosis considering factors related to their clinical behavior at "Dr. Jose Rafael Estrada Gonzalez" National Institute of Neurology and Neurosurgery, Havana, Cuba. Material and Methods: A descriptive and retrospective research was conducted. The study included a case series of 147 patients diagnosed with ALS by clinical and neurophysiological confirmation and images. The patients were treated in the multidisciplinary consultation in the period from October 2005 to October 2015. A total of 110 of them already died. Results: The disease most often occurs between the ages of 51 and 60. In the first 40 months, most of the patients in the series died, for a total of 80 people. The spinal clinical form predominated in males who had higher survival; the bulbar form prevailed in women. Most of the patients had no risk factors. Diabetes, arterial hypertension, ischemic cerebrovascular disease, neoplasms, hepatitis C, head trauma, bronchial asthma and ischemic heart disease stand out as comorbidities. There were cases of the disease within a single family. Conclusions: The greatest survival from the diagnosis of the disease was observed in the group between 51 and 60 years of diagnosis of the disease, some of them reaching up to 10 years. The general average of survival was between 2 and 5 years. It was lower in patients with comorbidities, family history and bulbar form. After evaluating the effectiveness of the treatment with Riluzole, the survival was not significant.

Comparative efficacy between ketamine, memantine, riluzole and d-cycloserine in patients diagnosed with drug resistant depression: a meta-analysis

Background: Glutamate modulators are having immense potential and are newer entities for treating drug resistant depression. The objectives were to generate statistical evidence on basis of existing data of ketamine, memantine, riluzole and d-cycloserine in resistant depression.Methods: A total of 14 RCTs following PRISMA guidelines and matching inclusion and exclusion criteria were collected of ketamine (5), memantine (3), riluzole (2) and d-cycloserine (4) vs placebo in drug resistant depression. Only RCTs with primary diagnosis of drug resistant depression (Previously on two standard antidepressant therapy) were included. Studies with treatment response rate, 50% reduction in total score of the depression rating scale-Montgomery-Åsberg Depression Rating Scale or the Hamilton Depression Rating Scale or Beck Depression Inventory was chosen as clinical outcome measure. RevMan 5.3 software was used for the analysis.Results: In ketamine group using random effect model SMD was 2.122 (95% CI 0.659-3.584). P-value was statistically significant (random effect p <0.005 and in fixed effect <0.001). In memantine group, using random effect model -0.963 was SMD and (95% CI -1.958-0.0324). P-value was <0.001, significant in fixed effect. In riluzole group, SMD was -0.564 with (95% CI -3.927-2.799) in random effect. P-value was 0.741. In d-cycloserine group SMD was 0.316 with (95% CI -1.252-1.885) in random effect. P-value was 0.690.Conclusions: Ketamine showed best efficacy followed by memantine. Riluzole and DCS as such have no efficacy although its acts by same glutamate pathway. More molecular based research is required in use of glutamate modulators in resistant depression.

Riluzole Selective Antioxidant Effects in Cell Models Expressing Amyotrophic Lateral Sclerosis Endophenotypes

OBJECTIVE: Until recently, riluzole was the only drug licensed for amyotrophic lateral sclerosis (ALS). In spite of its efficacy, the mechanism of action remains elusive, and both blocking of glutamate release and antioxidant properties have been postulated. Here we characterized human SH-SY5Y neuroblastoma cell lines, taking advantage of their insensitivity to excitotoxic insults, in order to selectively assess the presence of a direct antioxidant effect of riluzole. METHODS: SH-SY5Y cells, either parental or overexpressing the G93A SOD1 mutation, were exposed for 24 hours to the selected stimuli. RESULTS: Riluzole (1–10 μM) was able to counteract the effects of H₂O₂ exposure (200 μM/24 hr), limiting both cell death and whole-cell reactive oxygen species (ROS) increase. The same experiments were repeated using SH-SY5Y cells carrying the familial ALS-related G93A-SOD1 mutation and constitutively expressing two-fold increased whole-cell ROS levels with respect to wild-type cells: riluzole was ineffective in this paradigm. Analogously, riluzole was ineffective in preventing cell death induced by exposing SH-SY5Y cells to 3-morpholino-sydnonimine (SIN-1, 1.5 mM/24 hr), a reactive nitrogen species (RNS) donor. CONCLUSION: Our data support a direct antioxidant action of riluzole. Furthermore, the lack of efficacy of riluzole observed in the SOD1 cell model mirrors the lack of efficacy already demonstrated in cognate mouse models of ALS, plausibly reflecting differences in the underlying pathogenic mechanisms. Finally, riluzole inefficacy against nitrosative stress might support the idea that a combined therapeutic intervention may result more effective in ALS patients, as in the case of co-administration of edaravone, a drug known to reduce RNS.

Advance in Riluzole for Spinal Cord Injury (review) / 中国康复理论与实践

Spinal cord injury (SCI) is a disabling disease usually caused by trauma. The treatment and nursing of SCI patients has brought great economic burden to the society. This article introduced the mechanism of riluzole in treating spinal cord in-jury, including blocking Na+channels, reducing glutamate-mediated excitotoxicity, promoting the expression of neuro-trophic factors, and alleviating cellular oxidative stress damage and apoptosis, and the research progress on clinical trials of riluzole.

Epidemiological and clinical factors impact on the benefit of riluzole in the survival rates of patients with ALS / Impacto de fatores epidemiológicos e clínicos sobre o benefício do riluzol nas taxas de sobrevida de pacientes com ELA

ABSTRACT Objective To investigate the impact of epidemiological and clinical factors on the benefit of riluzole in patients with amyotrophic lateral sclerosis (ALS). Methods The survival rate of 578 patients with ALS (1999-2011) was analyzed by descriptive statistics and Kaplan-Meier curves. Considering the median of the sample survival time (19 months), patients were divided in two groups: below (B19) and above the median (A19). Kaplan-Meier curves compared the survival rates of patients treated with riluzole and with patients who did not take the medication. Results Riluzole increased the survival rates of patients with lower limb onset who were diagnosed after the first appointment in B19. Patients with bulbar onset and diagnosed on the first, or after the first appointment showed higher survival rates in A19. Males lived longer than females in both groups. Conclusion Epidemiological and clinical factors influenced the benefit of riluzole in the survival rates of patients with ALS.

RESUMO Objetivo Investigar o impacto de fatores epidemiológicos e clínicos sobre o benefício do riluzole em pacientes com esclerose lateral amiotrófica (ELA). Métodos A sobrevida de 578 pacientes com ELA (1999-2011) foi analisada por estatística descritiva e curvas de Kaplan-Meier. Considerando a mediana do tempo de sobrevida (19 meses), a amostra foi subdividida em dois grupos: sobrevida abaixo (B19) e acima de 19 meses (A19). As curvas de Kaplan-Meier compararam a sobrevida de pacientes tratados com riluzole e com pacientes que não receberam tratamento. Resultados O riluzole aumentou a sobrevida de pacientes com início nos membros inferiores e diagnosticados após a primeira consulta no grupo B19. Pacientes com início bulbar e diagnosticados na primeira/ após a primeira consulta apresentaram maior sobrevida em A19. Os homens apresentaram sobrevida maior do que as mulheres. Conclusão Foram encontradas diferenças epidemiológicas e clínicas no benefício do riluzole em pacientes com ELA.

Roles of glutamate transporter EAAT2 in occurrence and treatment of depression / 中国药理学通报

The glutamate transporter EAAT 2 ( rodent nomencla-ture GLT-1:glutamate transporter 1), which is a predominantly astroglial glutamate transporter in the hippocampus and the pre-frontal cortex , is responsible for the majority of extracellular glu-tamate uptake .The glutamate transporter EAAT 2 can decrease the high levels of glutamate in the synaptic cleft , avoiding gluta-matergic excitotoxicity to damage the glial cells and neurons . Currently, the transporter EAAT2 has become a research hotspot of depression .This article aims to summarize roles of glutamate transporter EAAT2 in the occurrence and treatment of depres-sion.

Efectos del riluzol en la evolución clínica y sobrevida de los pacientes con esclerosis lateral amiotrófica en Costa Rica / Effects of riluzole on clinical evolution and survival of patients with amyotrophic lateral sclerosis in Costa Rica

Justificación y objetivo:en la actualidad no se ha publicado un estudio que permita conocer el uso del riluzol en pacientes con esclerosis lateral amiotrófica en Costa Rica. El objetivo de este estudio fue evaluar el impacto del riluzol en la evolución clínica y sobrevida de los pacientes con esclerosis lateral amiotrófica atendidos en el Centro Nacional de Control del Dolor y Cuidados Paliativos.Materiales y métodos:estudio analítico, observacional y retrospectivo basado en los registros de los pacientes con esclerosis lateral amiotrófi atendidos en el Centro Nacional de Control del Dolor y Cuidados Paliativos en un período comprendido entre enero del 2009 y mayo del 2014. El análisis estadístico fue realizado en Microsoft Excel y SPSS versión 18. Para el análisis de sobrevida se utilizó estimaciones de Kaplan - Meier y se efectuó un análisis de sobrevida multivariado empleando una regresión de Cox.Resultados:se analizó 235 expedientes clínicos con el diagnóstico de esclerosis lateral amiotrófi que se encontraban en control en el Centro Nacional de Control del Dolor y Cuidados Paliativos, de los cuales 142 (60%) estaban en tratamiento con riluzol y 93 (40%) sin tratamiento con este medicamento, para una relación de 1,5 pacientes con riluzol por uno sin riluzol. Un 66% correspondía a hombres y un 34% a mujeres. Los pacientes en tratamiento con riluzol presentaron una mediana de sobrevida de 25,0 meses (IC95% 19,8 - 30,5 meses) y los pacientes que no recibieron tratamiento de 18,0 meses (IC95% 7,8 - 28,2 meses), con un valor de p para la comparación de las distribuciones de sobrevida de 0,17. Adicionalmente se encontró una diferencia estadísticamente signifi en el tiempo entre el inicio del tratamiento con riluzol y la colocación del PEG (p < =0,001). Los pacientes que recibieron el riluzol presentaron un promedio de tiempo mayor antes de requerir la colocación del PEG...

Background and aim:There is no study on the use of riluzol in patients with amyotrophic lateral sclerosis in Costa Rica. The objective of this study was to assess the impact of riluzole on clinical evolution and survival of patients with amyotrophic lateral sclerosis treated at the National Pain Control and Palliative Care Center.Materials and methods:An analytical, observational and retrospective study based on the records of patients with amyotrophic lateral sclerosis treated at the National Pain Control and Palliative Care Center between January 2009 and May 2014. The statistical analysis was performed using Microsoft Excel and SPSS version 18. Kaplan - Meier estimates were used for the analysis of survival estimates and a survival analysis was performed using a multivariate Cox regression.Results:We analyzed 235 medical records of patients diagnosed with ALS being controlled at the National Pain Control and Palliative Care Center, of which 142 (60%) were treated with riluzole and 93 (40%) did not take this drug, for a ratio of 1.5; 66% were men and 34% women. Patients treated with riluzole showed a median survival of 25.0 months (95% CI 19.8 to 30.5 months) and patients which didn´t receive treatment with riluzole showed a median survival of 18.0 months (95% CI 7.8 to 28.2 months), with a p-value of 0.17 for the comparison of survival distributions. In addition, a statistically significant difference in the time between the beginning of treatment with riluzole and placement of PEG (p-value 0.001) was found. Patients that received riluzole showed an increased average time before requiring the placement of PEG...

Research progress on pharmacological action of riluzole / 中国药学杂志

Riluzole is a benzothiazole compounds, and it is the only drug approved by FDA for the treatment of amyotrophic lateral sclerosis. By adjusting the concentration of glutamic acid and interfering with ion channels, riluzole has a wide range of pharmacology action, such as, regulating glutamate concentration, neuroprotective, cardioprotective, anti-depressants, anti-anxiety, analgesic and so on. In this paper, the pharmacological action of riluzole is summarized, aiming at providing help for its research and application.

A preliminary evaluation of comparative effectiveness of riluzole in therapeutic regimen for irritable bowel syndrome

Objective: To develop agents that are specifically effective in controlling the key disturbance of visceral hyperalgesia besides abating of associated multiple symptoms, and evaluate comparative effectiveness for IBS symptom relief for standard regimen (antispasmodic and probiotic) and add-on amitriptyine or riluzole regimens following two weeks administration.Methods:groups were studied. First group received standard treatment (mebeverine 200 mg twice daily and probiotic 200 mg twice daily). Second group received add-on amitriptyline 25 mg before bedtime, while the third group got add-on riluzole 50 mg twice daily. Overall gastrointestinal symptom rating scale improving symptoms and hospital anxiety depression scale improving associated psychological morbidity were employed as measures at induction and at two-week follow-up period. Individual symptom scores were also examined to define the outcome profiles.Results:108 patients with visceral hypersensitivity accompanying IBS, divided into three rating scale score, not the other two regimens. Pain relief was seen with both riluzole and amitriptyline regimens significantly superior to standard treatment regimen, but riluzole effect appeared specific and independent anxiolytic effect. Amitriptyline caused relief in diarrhea and did not benefit in constipation point to non-specific remedial role in IBS. Riluzole regimen resulted in significant reduction of overall gastrointestinal symptom Conclusions: Riluzole specifically relieves visceral hypersensitivity and is proved to be superior to current treatments in IBS patients. It appears a lead remedy based on glutamate transporter mechanisms in visceral hypersensititvity.

Study on Pharmacokinetics and in Vitro-in Vivo Correlation of Riluzole Tablets in Dogs / 医药导报

Objective To study the pharmacokinetic parameters of riluzole tablets and commercial riluzole capsules in Beagle dogs,and evaluate the correlation between the release rate in vitro and the absorption in vivo, and calculate the relative bioavailability of riluzole tablets. Methods Six Beagle dogs were treated with 50 mg of riluzole tablets or capsules,and then cross-treated by the other drug after 14-days wash out period. Blood concentration of riluzole was measured by high performance liquid chromatography ( HPLC ) . The atrioventricular model was used to calculate the pharmacokinetic parameters and Wanger-Nelson method was applied to assess the correlation between the release rate in vitro and the absorption in vivo. Results The t1/2 ,tmax ,Cmax ,AUC0-72 and AUC0-∞ in the tablet and capsule groups were (12. 43±3. 87) and (12. 57±3. 25) h,(6. 00±2. 60) and (6. 23±2. 72) h,(56. 24±16. 51) and (60. 82±18. 13) ng·mL-1 ,(1 255. 83±311. 39) and (1 283. 50±313. 81) ng·mL-1 ·h, (1 282. 57±322. 64) and (1 297. 22±297. 39) ng·mL-1 ·h,respectively. The relative bioavailability of capsules versus tablets was (105. 9±30. 6 )%. Conclusion HPLC method can be applied to measure the concentration of blood riluzole with little interference and high levels of repeatability and accuracy. The absorption in Beagle dogs between riluzole tablets and capsules was equal,and a good correlation between the in vivo absorption and in vitro release has been found in this study.

A preliminary evaluation of comparative effectiveness of riluzole in therapeutic regimen for irritable bowel syndrome

<p><b>OBJECTIVE</b>To develop agents that are specifically effective in controlling the key disturbance of visceral hyperalgesia besides abating of associated multiple symptoms, and evaluate comparative effectiveness for IBS symptom relief for standard regimen (antispasmodic and probiotic) and add-on amitriptyine or riluzole regimens following two weeks administration.</p><p><b>METHODS</b>108 patients with visceral hypersensitivity accompanying IBS, divided into three groups were studied. First group received standard treatment (mebeverine 200 mg twice daily and probiotic 200 mg twice daily). Second group received add-on amitriptyline 25 mg before bedtime, while the third group got add-on riluzole 50 mg twice daily. Overall gastrointestinal symptom rating scale improving symptoms and hospital anxiety depression scale improving associated psychological morbidity were employed as measures at induction and at two-week follow-up period. Individual symptom scores were also examined to define the outcome profiles.</p><p><b>RESULTS</b>Riluzole regimen resulted in significant reduction of overall gastrointestinal symptom rating scale score, not the other two regimens. Pain relief was seen with both riluzole and amitriptyline regimens significantly superior to standard treatment regimen, but riluzole effect appeared specific and independent anxiolytic effect. Amitriptyline caused relief in diarrhea and did not benefit in constipation point to non-specific remedial role in IBS.</p><p><b>CONCLUSIONS</b>Riluzole specifically relieves visceral hypersensitivity and is proved to be superior to current treatments in IBS patients. It appears a lead remedy based on glutamate transporter mechanisms in visceral hypersensititvity.</p>

Neurotransmitter evaluation in the hippocampus of rats after intracerebral injection of TsTX scorpion toxin

TsTX is an á-type sodium channel toxin that stimulates the discharge of neurotransmitters from neurons. In the present study we investigated which neurotransmitters are released in the hippocampus after TsTX injection and if they are responsible for electrographic or histopathological effects. Microdialysis revealed that the toxin increased glutamate extracellular levels in the hippocampus; however, levels of gamma-aminobutyric acid (GABA), glycine, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were not significantly altered. Neurodegeneration in pyramidal cells of hippocampus and electroencephalographic alterations caused by the toxin were blocked by pretreatment with riluzole, a glutamate release inhibitor. The present results suggest a specific activity of TsTX in the hippocampus which affects only glutamate release.

The Effect of Methylprednisolone and Riluzole on Axonal Growth after Acute Spinal Cord Injury in Rats / 대한정형외과학회잡지

PURPOSE: To determine the effect of methylprednisolone (MP) and riluzole administration on axonal growth after spinal cord injury (SCI) in rats. MATERIALS AND METHODS: Three Sprague Dawley rats (SD rat) served as controls (average 24 weeks of age) and 24 SCI SD rats scoring below 7 points on on Basso, Beattie, and Bresnahan open field test served as test subjects (total 27 SD rats; mean weight 581 g, range=427-613 g). Test subjects were divided into two groups of 12 subjects each. Group I was injected with saline (1 ml/kg) and group II was injected with MP (300 mg/kg) and riluzole (5 mg/kg) intraperitoneally. Four SD rats were sacrificed in each group at the following time points after SCI: days 1, 4, and 7. We completed behavioral testing, immunohistochemical staining and RT-PCR for chondroitin sulfate proteoglycans (CSPG), and microarrays for c-JUN, ATF-2, p53, and Elk-1. RESULTS: On behavioral testing, group II showed superior results at only day 4 after SCI (p<0.05). On RT-PCR for CSPG, optical densities were 2.06 (ratio=Group I/Group II) and 2.11 at days 4 and 7, respectively. Microarray showed that lower expression of c-JUN in group II during the entire period (p< 0.05). ATF-2 showed lower expression in group II at days 4 and 7 (p<0.05). p53 showed lower expression in group I at day 1 (p<0.05). Elk-1 showed lower expression in group I at day 1 (p<0.05) and in group II at day 7 (p<0.05). CONCLUSION: Simultaneous administration of MP and riluzole led to various changes in the MAPK pathway, and decreased CSPG. Therefore, this method has a protective effect on axonal regeneration after SCI in an SD rat model.

Outcome of sporadic amyotrophic lateral sclerosis treated with non-invasive ventilation and riluzole / Sobrevida en pacientes con esclerosis lateral amiotrófica esporádica tratados con ventilación no invasiva y riluzole

Sporadic amyotrophic lateral sclerosis (sALS) is a progressive degenerative motor neuron disorder lacking specific treatment. Riluzole is the only drug able to modestly slow down the course of the disease. Respiratory insufficiency is the main cause of death; non invasive ventilation (NIV) has shown to improve survival. Our aim was to evaluate the effect of NIV and riluzole on survival. Ninety seven patients with a diagnosis of sALS were assessed and followed up for 60 months. Twenty nine patients received NIV and 68 did not (nNIV). Overall median survival In the NIV group was 15.41 ± 7.78 months vs. 10.88 ± 7.78 months in the nNIV group (p= 0.028). Median survival time was not different in patients receiving riluzole (n=44), as compared with those who did not (n=53), although at month 4th and 5th riluzole treated patients showed a modest benefit. In those who only received NIV (n=11) or only riluzole (n=26), survival time was 13.45 ± 13.44 months and 11.19 ± 7.79 months, respectively. Patients who received both NIV and riluzole (n=18) had a median survival time of 16.61 ± 10.97 months vs. 10.69 ± 7.86 months for those who received only supportive treatment (n=42) (p= 0.021). NIV improved survival in our series of patients. Riluzole did not show any significant impact on survival when employed as the only therapy. Patients receiving both treatments simultaneously had a significant longer survival.

La esclerosis lateral amiotrófica esporádica (sALS) es una enfermedad degenerativa para la que no existe tratamiento etiológico eficaz. El riluzole prolonga poco la sobrevida. La principal causa de muerte es la insuficiencia respiratoria. Uno de los tratamientos para esta última es la ventilación asistida no invasiva (NIV) con equipos de doble nivel de presión. El objetivo de este trabajo fue determinar el impacto en la sobrevida de estos enfermos combinando ventilación no invasiva y riluzole. Se evaluaron y siguieron durante 60 meses 97 pacientes con diagnóstico de sALS, según criterios definidos en El Escorial modificados, y fueron seguidos por 60 meses. Veintinueve pacientes recibieron NIV y 68 no (nNIV). En el grupo NIV la sobrevida media fue de 15.41 ± 7.78 meses vs. 10.88 ± 7.78 meses en nNIV (p= 0.028). La sobrevida media de los pacientes que recibieron riluzole (n=44) no fue diferente de la que no lo recibieron (n=53), aunque en el 4° y 5° mes los pacientes tratados con riluzole mostraron un escaso beneficio. Los pacientes que recibieron NIV y riluzole (n=18) tuvieron una sobrevida media de 16.61 ± 10.97 meses vs. 10.69 ± 7.86 meses para los que sólo recibieron tratamiento sintomático (n=42) (p= 0.021). La NIV prolongó significativamente la sobrevida en este grupo de pacientes. El riluzole, empleado como única terapéutica, no lo hizo. Los pacientes que combinaron los dos tratamientos tuvieron la mayor sobrevida.

The Effects of Riluzole and Trolox in Transient Retinal Ischemia

PURPOSES: To evaluate the effect of riluzole (water soluble vitamin E, antioxidant) and trolox(glutamatergic neurotransmission antagonist) in transient retinal ischemia. METHODS: The effects of two drugs were investigated in a gerbil model of retinal ischemic injury. Retinal ischemia was induced by clipping both common carotid arteries for 15 minutes. In group I (10 eyes), 10 gerbils received an intraperitoneal injection of the saline, and in group II (10 eyes), riluzole was injected 30 minutes before ischemia and 30 minutes after the end of the ischemic insult and once daily during the recovery period. In group III (10 eyes), trolox was injected and in group IV (10 eyes), riluzole and trolox were injected in a same manner. Electroretinograms were recorded before ischemia and after 1 hour, 2 days, and 7days of reperfusion. Retinas were harvested for histopathology (hematoxyline-eosin staining and Tdt-dUTP terminal nick-end labeling method). RESULTS: Ischemia for 15 minutes caused reduction of a- and b- waves of the electroretinogram. Treatments with riluzole or trolox significantly enhanced the recovery of the reduced a-and b-waves after reperfusion. Combined treatment with riluzole and trolox also enhanced the recovery of the reduced a-and b-waves, but synergistic effect was not observed. Riluzole and trolox also prevented or attenuated ischemia induced cell death (necrosis and apoptosis). CONCLUSIONS: Riluzole and trolox acted in vivo as a potent neuroprotective agents against transient retinal ischemic model. Therefore, riluzole and trolox may be a major drug for use in the protection against retinal ischemic injury.

Unscrambling the international clinical guidelines of amyotrophic lateral sclerosis / 中国实用内科杂志

Early diagnosis and symptomatic therapy of amyotrophic lateral sclerosis(ALS)can profoundly influence care and quality of life of the patient and relatives,and may increase survival time.Medication with riluzole should be initiated as early as possible.PEG is associated with improved nutrition and should be inserted early.Noninvasive positive pressure ventilation improves survival and quality of life.Palliative end-of-life care should be provided to ALS patient.

Antagonism of Dextromethorphan and Riluzole to Neurotoxicity Induced by Methylmercury in Rats / 环境与健康杂志

Objective To observe the adverse effect of methylmercury on the cortex and cerebellum respectively as well as to approach the antagonisms of dextromethorphan(DM) and riluzole to the mercury-induced neurotoxicity.Methods Twenty-eight Wistar rats were randomly divided into 4 groups by weight,7 in each.The first group was the control group and the second group was methylmercuric chloride(MMC) group.The third and fourth groups were DM and riluzole group respectively.Both of the former groups were subcutaneously injected with saline.The third and fourth groups were subcutaneously injected with 13.5 ?mol/kg DM and 21.35 ?mol/kg respectively every other day.Two hours later,the animals in the control group were intraperitoneally given the injection of saline.From the second to fourth groups were injected with 12.0 ?mol/kg MMC.The administration of MMC above was given five times a week(from Monday to Friday),for 4 weeks as well as the administration of DM and riluzole every other day before injected with MMC(on Monday,Wednesday and Friday).Twenty-four hours after the last injection,7 rats in each group were sacrificed.The contents of Hg,Ca2+-ATPase in the cerebellum were determined.Results In MMC group,the contents of Hg,Glu and the content of Gln were decreased,the activities of SDH,Na+-K+-ATPase and Ca2+-ATPase were decreased compared with the control group.Compared with MMC group,in DM and riluzole groups,the contents of Hg,Glu decreased,the content of Gln increased,moreover,the activities of SDH,Na+-K+-ATPase and glutamate(Glu),glutamine(Gln) in the rat cortex and the activities of SDH,Na+-K+-AT Pase and Ca2+-AT Pase increased significantly.Conclusion "Glu-Gln Cycle" can be destroyed by MMC,DM and liluzole present some antagonistic effects on MMC-indused neurotoxicity in rats.

Determination of the Riluzole Concentration in Blood Plasma by RP-HPLC / 中国药房

OBJECTIVE:To develop the method for the determination of riluzole concentration in blood plasma.METH?ODS:Riluzole was extracted with diethyl ether.The residues were analyzed with a reverse phase HPLC system(Diamonsil TM C 18 column,250mm?4.6mm,5?m),with mobile phase of MeOH-0.03mol/L and NH 4 H 2 PO 4 (80∶20,V/V),UV detection wave length of265nm,flow rate of0.8ml/min.RESULTS:The linear coverage of Riluzole was5～1000ng/ml;the lowest detectable concentration was5ng/ml.The average recoveries of riluzole were99.51%,95.74%and97.12respectively.The within-day and between-day relative standard deviations were1.17%、6.48%(n=5)respectively.CONCLUSION:The met_ hod is sensitive,accurate,simple and reliable,and it can be applied to phamacokinetic studies.