Effects of galantamine and galantamine combined with nimodipine on cognitive speed and quality of life in mixed dementia: a 24-week, randomized, placebo-controlled exploratory trial (the REMIX study) / Efeitos da galantamina e da galantamina combinada à nimodipina sobre a velocidade de processamento cognitivo e qualidade de vida na demência mista: ensaio clínico exploratório, randomizado e controlado com placebo (estudo REMIX)

The effects of galantamine (GAL) on quality of life (QoL) and cognitive speed, as well its effects combined with nimodipine (NIM) in Alzheimer disease (AD) with cerebrovascular disease (mixed dementia), have not been explored. Method : Double-blind, placebo-controlled, multicenter Brazilian trial, studying the effects of GAL/NIM vs. GAL/placebo (PLA) in mild to moderate mixed dementia. Patients were randomized to receive GAL/NIM or GAL/PLA for 24 weeks. Primary efficacy measures were changes on a computerized neuropsychological battery (CNTB) and QoL Scale in Alzheimer's Disease (QoL-AD) from baseline to week 24. Results : Twenty-one patients received at least one drug dose (9 GAL/NIM and 12 GAL/PLA). Groups were matched for age, sex, education, cognitive and QoL scores at baseline. No significant differences were observed between groups on primary or secondary measures. QoL and cognitive performance showed significant improvement (p<0.05) from baseline when all GAL-treated patients were analyzed. Adverse events were predominantly mild to moderate. Conclusion : GAL treatment improved QoL in mixed dementia, in addition to its previously known cognitive benefits. The combination GAL/NIM was not advantageous. However, the small sample size precludes any definitive conclusions. Trial registered at ClinicalTrials.gov: NCT00814658 .

Os efeitos da galantamina (GAL) sobre qualidade de vida (QdV) e velocidade de processamento cognitivo, bem como da combinação com nimodipina (NIM) no tratamento da doença de Alzheimer (DA) com doença cerebrovascular (demência mista) ainda não foram investigados. Método : Estudo multicêntrico brasileiro, duplo-cego, controlado com placebo, avaliando os efeitos de GAL/NIM x GAL/placebo (PLA) na demência mista leve a moderada. Pacientes receberam tratamento com GAL/NIM ou GAL/PLA por 24 semanas. Medidas de eficácia primária foram as variações no desempenho em bateria de testes neuropsicológicos computadorizados e na escala QdV-DA ao final do estudo. Resultados : Vinte um pacientes receberam pelo menos uma dose da droga (9 GAL/NIM e 12 GAL/PLA). Os grupos foram emparelhados por idade, sexo, escolaridade, escores cognitivos e de QdV na linha de base. Não foram observadas diferenças significativas entre os dois grupos nas medidas de eficácia primária e secundária. Na avaliação de todos os pacientes que receberam GAL, houve melhora significativa (p<0,05) em QdV-DA e desempenho cognitivo. Os eventos adversos foram predominantemente leves a moderados. Conclusão : O tratamento com GAL proporcionou melhora da QdV na demência mista, além dos benefícios cognitivos previamente conhecidos. A combinação GAL/NIM não foi vantajosa. O reduzido tamanho amostral impede conclusões definitivas. .

Evaluación de la efectividad de la nimodipina en el tratamiento del vértigo de origen periférico: reporte preliminar / Evaluation of the effectiveness of nimodipine in the treatment of vertigo of peripheral origin: preliminary report

El vértigo es un síntoma que se caracteriza por la ilusión de movimiento. Esto afecta tanto el bienestar individual como la capacidad para realizar las actividades propias de la vida cotidiana, ejerciendo un impacto negativo sobre la calidad de vida, por lo tanto es importante encontrar una terapia efectiva y cómoda que permita al paciente incorporarse a las labores de la vida diaria lo mas rápido posible y con la mejor calidad de vida. Métodos: Se evaluó la efectividad en el tratamiento del vértigo de origen periférico de dos formulaciones de nimodipina, la nimodipina convencional de administración tres veces al día (Nimotop® 30 mg) versus la nimodipina 90 mg. AP de administración una vez al día (Tropocer®). Se realizó un estudio clínico prospectivo, aleatorizado, doble ciego, doble simulado (doble dummy), multicéntrico nacional, de grupos paralelos, donde se incluyeron pacientes con vértigo de origen periférico, definido como una puntuación mayor o igual a 7 en el Vertigo-Dizziness Differential Diagnosis Score (VDDDS)¹. Los pacientes fueron evaluados mediante la escala Índice de Severidad del Vértigo2 y el Índice de Discapacidad Vestibular. Resultados: En el grupo de nimodipina AP el Índice de Severidad del Vértigo² disminuyó en un cincuenta por ciento en el 38% de los pacientes a los 14 días, en 53% y 92% a las 4 y 8 semanas respectivamente. El Índice de Discapacidad Vestibular disminuyó en un 50% a los 14 días en el 31% de los pacientes y en 77% y 92% a las 4 y 8 semanas respectivamente. En el grupo de nimodipina convencional el Índice de Severidad del Vértigo disminuyó en un 50% en: 25% de los pacientes a los 14 días, en 67% y 93% a las 4 y 8 semanas respectivamente. El índice de Discapacidad Vestibular disminuyó en 50% a los 14 días en el 30% de los pacientes y en 78% y 100% a las 4 y 8 semanas respectivamente, sin diferencias significativas entre los grupos

Vertigo is a symptom that is characterized by the illusion of movement. It affects both individual welfare and the ability to perform activities of daily living, having a negative impact on quality of life, so it is important to find a comfortable and effective therapy that allows the patient to join the work of the daily life as soon as possible and with the best quality of life. Methods: We evaluated the effectiveness in the treatment of vertigo of peripheral origin of two formulations of nimodipine: conventional nimodipine of administration three times daily (30 mg Nimotop®) versus nimodipine 90 mg. Extender Release (ER) administration once day (ER Tropocer® 90 mg). We performed a prospective, randomized, double-blind, double dummy, national multicenter parallel-group, clinical study which included patients with vertigo of peripheral origin, defined as a score greater than or equal to 7 at the Vertigo-dizziness Differential Diagnosis Score (VDDDS). Patients were evaluated with the scale Index of Severity of Vertigo and Vestibular Disability Index. Results: In the nimodipine ER group, the index of severity of vertigo decreased 50%: in 38% of patients to 14 days in 53% and 92% at 4 and 8 weeks respectively. The vestibular disability index decreased 50% to 14 days in 31% of patients and in 77% and 92% at 4 and 8 weeks respectively. In the nimodipine Conventional group, the index of severi-ty of vertigo decreased in 50% in 25% of patients to 14 days in 67% and 93% at 4 and 8 weeks respectivelyAU)

Subarachnoid haemorrhage: possibly caused by the illegitimate use of sildenafil citrate.

Sildenafil (Viagra) has been developed as a drug to treat male impotence. It has also been used to reduce symptoms (e.g. improved exercise capacity) in patients with pulmonary arterial hypertension. A case of subarachnoid haemorrhage (SAH) following the illicit use of sildenafil is reported.

Nimodipine is more effective than nifedipine in attenuating morphine tolerance on chronic co-administration in the rat tail-flick test.

Opioids, when co-administered with L-type calcium channel blockers (L-CCBs) show morphine like higher antinociceptive effect. This antinociceptive effect has been further investigated using a different experimental paradigm. The effect of two different L-CCBs (nifedipine and nimodipine) on morphine-induced antinociception was studied by the tail-flick test (40 min after morphine administration) in adult Wistar rats. A fixed-dose of nimodipine or nifedipine (2 mg/kg, once daily) was combined with a fixed dose of morphine (10 mg/kg, twice daily) for 10 days. Co-administration of L-CCBs significantly increased the antinociceptive effect of morphine, even 12 hr after administration. Also, nimodipine was more effective than nifedipine. Nimodipine was further studied using a higher and escalating doses of morphine (20-30 mg/kg twice daily for 14 days). Nimodipine increased the antinociceptive effect of morphine in the latter part of the study (days nine to fourteen) though significant difference was observed on 11th evening and 12th morning. No obvious adverse effects were observed in the present study. The results show for the first time that nimodipine is more effective than nifedipine and that these L-CCBs continue to be effective, even 12 hr after administration in the tail-flick test.

Comporación de dos formulaciones de nimodipina en pacientes de edad avanzada con deterioro cognitivo estudio multicéntrico nacional aleatorizado doble ciego / Comporación two nimodipine formulations in elderly patients with cognitive impairment randomized national multicentre double-blind

Evaluar la seguridad y la efectividad en deterioro cognitivo de pacientes con edades entre 55 a 80 años de dos formulaciones de nimodipina: 120 mg de liberación programada (LP) una toma diaria y nimodipina 30 mg de liberación inmediata (LI), 4 tomas diarias. Estudio doble ciego, doble simulado, aleatorio, con pacientes con MMST entre 15 y 24. Estos recibieron las 4 semanas iniciales placebo, luego 12 semanas doble ciego, nimodipina LI activo cuatro tomas diaria, o nimodipina LP activo en una toma diaria. Fueron evaluados a las 12 semanas de tratamiento mediante MMST, escala de Barthel, impresión clínica de cambio" por el médico y el paciente. Ingresaron 69 pacientes, finalizaron el 95.6 por ciento. Treinta y tres con nimodipina LP y treinta y tres con nimodipina LI. Con nimodipina LI, 79 por ciento mejoraron el score de MMST; 78 por ciento notaron mejoría y en 84 por ciento la mejoría fue observada por el médico. Cinco pacientes presentaron reacciones adversas (lipotimia, dos con erupción cutánea, cefalea y epigastralgia), dos suspendieron el tratamiento. En nimodipina LP, 94 por ciento mejoraron el MMST, 94 por ciento dijeron sentirse mejor y en el 91 por ciento, la mejoría fue observada por el médico. Tres (3) pacientes presentaron reacciones adversas (acidez gástrica, hipotensión y mareos), uno suspendió el tratamiento. La nimodipina 120 mg. LP administrada una vez al día y la nimodipina LI 30 mg. administrada cuatro veces al día mejoran el deterioro cognitivo en la edad avanzada, siendo bien toleradas.

Enhanced analgesic effect of morphine-nimodipine combination after intraspinal administration as compared to systemic administration in mice.

Calcium plays an important role in the pathophysiology of pain. A number of studies have investigated the effect of L-type calcium channel blockers on the analgesic response of morphine. However, the results are conflicting. In the present study, the antinociceptive effect of morphine (2.5 microg) and nimodipine (1 microg) co-administered intraspinally in mice was observed using the tail flick test. It was compared to the analgesic effect of these drugs (morphine - 250 microg subcutaneously; nimodipine - 100 microg intraperitoneally) after systemic administration. Nimodipine is highly lipophilic and readily crosses the blood brain barrier. Addition of nimodipine to morphine potentiated the analgesic response of the latter when administered through the intraspinal route but not when administered through systemic route. It may be due to direct inhibitory effect of morphine and nimodipine on neurons of superficial laminae of the spinal cord after binding to mu -opioid receptors and L-type calcium channels respectively.

Evaluation of nimodipine in the treatment of severe diffuse head injury: a double-blind placebo-controlled trial.

AIMS: The aim of this study was to establish whether nimodipine given orally soon after severe diffuse head injury for a period of three weeks improved outcome. MATERIAL AND METHODS: The present report analyzes the results of a prospective randomized double-blind placebo-controlled trial of nimodipine in 97 severe head injury patients (GCS Score < or =8) treated at the Department of Neurosurgery, NIMHANS, between January 1995 and June 1996. The patients were randomly assigned to two groups which were matched for age, sex, mode of injury, time interval from injury to admission, neurological status and CT scan findings. One group was given nimodipine 30 mg Q6H and the other group was given a placebo. The outcome of these patients at 6 months was evaluated using the Glasgow Outcome Score by and a psychologist. RESULTS: Results showed no significant difference in the functional and psychological outcome between the two groups, even in patients with subarachnoid hemorrhage. No adverse drug events were recorded. CONCLUSION: Oral nimodipine given for three weeks does not improve outcome in patients with severe diffuse head injury.

Manejo clínico del traumatismo encefalocraneano grave / Clinical management of the severe encephalocranial injuries

El TEC es la causa más frecuente de mortalidad e invalidez en niños y adultos jóvenes. Si bien el neurocirujano no puede prevenir los daños traumáticos primarios, la atención está dirigida a la prevención de los daños secundarios causados por hipotensión, hipoxemia y la prevención de complicaciones intracraneanas y sistémicas. Será fundamental el manejo de la presión intracraneana (PIC) con el fin de mantener una presión de perfusión cerebral (PPC) adecuada. Requiriendo todo paciente con un puntaje de 8 o menos en la escala de coma de glasgow (GCS) monitoreo de su PIC. Descartada la presencia de una lesión susceptible de manejo quirúrgico, las medidas indicadas son la hiperventilación moderada (pCO230-35 mm Hg) y el uso de sustancias hiperosmolares (manitol). En pacientes refractarios a estas medidas deberá discutirse como medida adicional el coma barbitúrico y la craneotomía decompresiva

Anticonvulsant profile of nimodipine and nitrendipine against pentylenetetrazole induced seizures in rats.

The activity of nimodipine and nitrendipine against pentylenetetrazole (PTZ) induced seizures in Albino rats was studied alone and in combination with valproate. The median effective dose [ED50] of valproate, nimodipine and nitrendipine were initially determined. All the 3 drugs were injected i.p. 30 min before the induction of seizures. Seizures were induced by PTZ 85 mg/kg i.p., and subsequently the effect of combining ED50 doses of nimodipine and nitrendipine with ED50 dose of valproate was evaluated. ED50 of valproate and nitrendipine were 129 and 2.5 mg/kg respectively. ED50 of nimodipine could not be established since a dose-response relationship was not obtained. Hence, for the purpose of combination studies, 4 mg/kg of nimodipine was used. Both nimodipine (4 mg/kg) and nitrendipine (2.5 mg/kg) decreased the ED50 of valproate from 129 to 40 mg/kg. Both nimodipine and nitrendipine potentiate the activity of valproate against PTZ induced seizures and can be considered as potential adjuvant anticonvulsants which merit further study.

Effect of nimodipine on the efficacy of commonly used antiepileptic drugs in rats.

Effect of nimodipine was studied alone and in combination with phenytoin and valproate in maximal electroshock seizures in rats. The test drug was injected i.p. and seizures elicited by a 60 Hz alternating current of 150 mA intensity for 0.25 sec duration through corneal electrodes. The median effective dose (ED50) of phenytoin, valproate and nimodipine were found to be 13, 255 and 4 mg/kg respectively. Addition of ED50 of nimodipine to ED50 of phenytoin and valproate produced an additive effect. Addition of ED25 of nimodipine to ED25 of phenytoin and valproate produced asynergistic effect. Our results show that addition of nimodipine significantly potentiates the anticonvulsant efficacy of phenytoin and valproate.

Emprego da nimodipina (oxigen) como protetor cerebral na cirurgia de revascularizaçäo do miocárdio com circulaçäo extracorpórea em pacientes idosos / Use of nimodipin (oxigen) as a cerebral protector in myocardial revascularization surgery with extracorporeal circulation in elderly patients

Aproximadamente 5 por cento dos pacientes submetidos a cirurgia cardíaca com auxilio da circulaçao extracorpórea apresentaram problemas neurológicos. Avaliando funçoes neuropsíquicas, as alteraçoes atingem de 5O por cento a 7O por cento dos casos. Os idosos sao mais vulneráveis; nestes, a freqüência de acidente vascular cerebral (AVC) aproxima-se dos 9 por cento. Considerando que a populaçao envelhece a um ritmo acelerado e que o coronariopata freqüentemente passa dos 65 anos de idade, é fundamental pesquisar meios profiláticos para diminuir esta incidência. Este é um estudo piloto, duplo cego, randomizado e controlado com 64 pacientes, 30 no grupo nimodipina e 34 no Grupo placebo. As variáveis demográficas e diagnósticas pré-operatórias foram homogêneas, com exceçao da incidência de isquemia cerebral transitória. O Grupo nimodipina, mesmo com programaçao cirúrgica e evoluçao intra e pós-operatória mais complicadas, apresentou menor número de casos neurológicos. No Grupo nimodipina foram constatados 3 casos de confusao mental e, no Grupo placebo, além de 3 casos de confusao mental, foram diagnosticados mais 2 casos de sonolência e 1 AVC isquêmico com seqüela. No total, foram 3 (lO por cento) casos em 30 pacientes no Grupo nimodipina, e 6 (l7,64 por cento) em 34 pacientes no Grupo placebo, caracterizando uma reduçao de 76,4 por cento. LEGAULT et al. relatam uma elevada mortalidade de pacientes em uso de nimodipina, quando operados para troca valvar, causada, principalmente, por hemorragia. Nós nao encontramos esta correlaçao. A mortalidade hospitalar é similar em ambos os grupos (l paciente em cada) e o sangramento nao é estatisticamente diferente (l caso de hemorragia importante no Grupo nimodipina). No seguimento até 41 meses, a mortalidade no Grupo placebo foi maior (4 pacientes) que no Grupo nimodipina (l paciente).

Use of calcium channel blockers in acute ischemic cerebrovascular disease.

Many studies have shown that increased intracellular concentration of calcium ions is an important factor influencing neuronal damage in acute ischemic cerebrovascular disease (ICVD) and administration of calcium-channel blockers during the "open therapeutic window" have beneficial cytoprotective effects. In a prospective ICVD study we administered dihydropyridine compound "nimodipine" (1.5 to 2.0 mg/kg/day) either orally or as continuous intravenous drip round the clock for the first three days followed by oral therapy along with standard treatment after the diagnosis of a stroke was confirmed by CT Scan. The "ICVD" control cases received best medical care (BMC). The degree of functional neuronal recovery (using modified Mathew's scale) was assessed after three weeks of therapy. Our study shows significant improvement in the quality of neurologic recovery though there was no change in mortality rate in both the groups.

Hipotensión controlada con nimodipina en pacientes a los que se realiza neurocirugía / Controlled hypotension by nimodipine in patients submitted to neorusurgery

Con la perfusión parenteral de nimodipina al 0.000165 fue factible abatir las cifras tensionales en 24 pacientes de uno y otro sexo a quienes se les hicieron procedimientos neuroquirúrgicos bajo anestesia general balanceada. El hipotensor permite un flujo sanguíneo sistémico y endocraneano adecuado y se sabe que tiene efecto neuroprotector. En ningún paciente se hicieron aparentes signos de complicaciones neurológicas, cardiocirculatorias ni metabólicas

Tratamiento crónico con nimodipina en el accidente cerebro-vascular (ACV) / Chronic treatment with nimodipina in the brain-vascular stroke

Investigaciones recientes sugieren que las concentraciones elevadas de calcio intracelular puede estar implicadas en la muerte neuronal después de la isquemia. Ventiocho pacientes con accidente cerebro-vascular agudo permanente fueron incluidos en un ensayo clínico prospectivo, bodle ciego y de asignación al azar, para determinar si el tratamiento con el calcio antagonista nimodipina, reduciría su mortalidad y déficit neurológico. A todos los pacientes les fue administrado tratamiento estandarizado. Además, 14 pacientes recibieron diariamente 120mg de nimodipina vía oral dividida en 4 dosis (grupo tratado) durante 180 días. El análisis de la terapéuta se basó en la utilización de tres sistemas de evaluación (Escala Mathew, Barthel y Orgogozo). La comparación de los resultados en el grupo control con aquellos del grupo nimodipina revelaron una diferencia significativa en favor de la nimodipina a los 28 días de tratamiento (Barthel p<0.02; Orgogozo p<0.03) y a los 6 meses (Mathew p<0.05; Barthek p<0.03 y Orgogozo p<0.006). Todos los casos de fallecimiento ocurrieron en los primeros 28 días, completando un total de 10 pacientes, 6 (42.8 por ciento) en el grupo stándar 4 (28.5 por ciento) en el grupo nimodipina. Los efectos colaterales fueron de menor importancia y de ninguna relevancia clínica

Isquemia y perfusión hepatica en ratas efecto de la nimodipina y la clorpromazina / Ischemia and hepatic reperfussion in rats: effect of nimodipine and chlopromazine

El aumento del calcio iónico intracelular constituye uno de los fenómenos involucrados en la lesión celular por isquemia y reperfusión. Utilizando un modelo experimental de isquemia hepática segmentaria en ratas se evalúan los efectos de la nimodipina y la clorpromazina, dos drogas que regulan elcalcio intracelular. Como indicadores se utilizan LDH, TGO y TGP, antes de la isquemia y a las 48 horas; el experimento incluye cuatro (4) grupos de ratas: un grupo para cada droga, un grupo control con isquemia sin tratamiento y un grupo de operación simulada. La LDH muestra valores basales elevados que descienden en todos los grupos con isquemia y se mantienen en el grupo de operación simulada. La TGO se eleva en el grupo control y se mantiene estable en los otros grupos. La TGP se eleva en el grupo control y se mantiene estable en los otros grupos. Esto sugiere un efecto citoproctector de las drogas antes mencionadas en las condiciones de este experimento