Therapeutic Results with Nimodipine in Primary Degenerative Dementia and Multi-Infarct Dementia

Fischhof, Peter K.; Wagner, Gabriela Peretti; Littschauer, L.; Rüther, E; Apecechea, M.; Hiersemenzel, Reinhard; Röhmel, Jobst; Hoffmeister, F. S.; Schmage, N.

doi:10.1007/978-3-642-46658-8_27

Cited by 30 publications

(14 citation statements)

References 7 publications

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“…Based on the results presented above, highlighting the therapeutic benefits of rivastigmine on cognitive performance, disease severity and ADL in AD patients with vascular risk factors, the concern of treating patients with rivastigmine who may have undetectable vascular changes in addition to AD with a cholinesterase inhibitor may be attenuated. It is important to note, however, that no drug therapy has been established to date to treat the cognitive impairment associated with vascular dementia, although compounds including pentoxifylline (Black et al, 1992), nimodipine (Fishhof et al, 1989), propentofyllin (Marcusson, 1995) and hydergine (Schneider and Olin, 1994) have been studied. Their effects appear to be modest, with the most clinically significant effects having been observed in subgroups of patients with VaD.…”

Section: Discussionmentioning

confidence: 99%

An efficacy and safety analysis of Exelon^® in Alzheimer’s disease patients with concurrent vascular risk factors

Kumar¹,

Anand

Messina

et al. 2000

Euro J of Neurology

150

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We evaluated the efficacy and safety of the centrally acting cholinesterase inhibitor, rivastigmine tartrate, for patients with mild to moderately severe Alzheimer's disease (AD) with or without concurrent vascular risk factors (VRF). Patients (45-90 years of age) were randomized to placebo (n = 235), low-dose rivastigmine (1-4 mg/day, n = 233), or high-dose rivastigmine (6-12 mg/day, n = 231) for 26 weeks. Efficacy measures included the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), the Clinician's Interview Based Impression of Change (CIBIC-Plus), the Progressive Deterioration Scale (PDS), the Global Deterioration Scale (GDS), and the Mini-Mental State Examination (MMSE). For efficacy and safety analysis, patients were categorized by baseline Modified Hachinski Ischemic Score (MHIS) for the determination of VRF (MHIS > 0: presence of VRF; MHIS = 0: absence of VRF). As early as 12 weeks, the mean change from the baseline ADAS-Cog score was significantly different for those patients treated with high-dose rivastigmine compared with placebo controls in both MHIS categories. However, the treatment difference between high-dose rivastigmine and placebo at each time-point was larger for patients with MHIS > 0. The proportion of responders was significantly greater in the high-dose rivastigmine group for each level of improvement. No differences were noted between treatment groups regarding safety evaluations. Rivastigmine is effective in both categories of patients, and those with VRF experience greater clinical benefit (cognition, activities of daily living, and disease severity).

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Section: Discussionmentioning

confidence: 99%

An efficacy and safety analysis of Exelon^® in Alzheimer’s disease patients with concurrent vascular risk factors

Kumar¹,

Anand

Messina

et al. 2000

Euro J of Neurology

150

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“…Nimodipine has also been used in the treatment of ischemic stroke (Svetyi et al, 2002;Sobrado et al, 2003;Fogelholm et al, 2004), multi-infarct dementia (Fischhof et al, 1989;Pantoni et al, 2000) and migraine prophylaxis (Evers, 1999;Victor, Ryan, 2003).…”

Section: Introductionmentioning

confidence: 99%

Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

Nascimento

Moraes

Bezerra

et al. 2010

Braz. J. Pharm. Sci.

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To develop and validate a rapid, specific and highly sensitive method to quantify nimodipine in human plasma using dibucaine as the internal standard (IS). The analyte and IS were extracted from plasma samples by liquid-liquid extraction using hexane-ethyl acetate (1:1 v/v). The chromatographic separation was performed on a Varian ® Polaris C18 analytical column (3 mm, 50 x 2.0 mm) and pre-column Securityguard TM C18 (4.0 x 3.0 mm) with a mobile phase of Acetonitrile-Ammonium acetate 0.02 ml/L (80:20v/v). The method had a chromatographic run time of 4.5 min and linear calibration curve over the range of 0.1-40 ng/mL (r > 0.9938). The limit of quantification was 100 pg/mL. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. This validated method was successfully applied in determining the pharmacokinetic profile of nimodipine tablets of 30 mg administered to 24 healthy volunteers. The proposed method of analysis provided a sensitive and specific assay for nimodipine determination in human plasma. The time for the determination of one plasma sample was 4.5 min. This method is suitable for the analysis of nimodipine in human plasma samples collected for pharmacokinetic, bioavailability or bioequivalence studies in humans.Uniterms: Nimodipine/determination in plasma. Nimodipine/pharmacokinetic profile. Nimodipine/ quantitative analysis. Pharmacokinetics/method validation.Um método rápido, específico e sensível para quantificar nimodipino em plasma humano usando dibucaína como padrão interno (IS) é descrito. O analito e o IS foram extraídos das amostras de plasma por extração líquido-líquido usando hexano-acetato de etila (1:1 v/v). A separação cromatográfica foi realizada utilizando-se uma coluna analítica C18 Varian ® Polaris (3 mm, 50 x 2,0 mm) e uma pré-coluna Securityguard TM C18 (4,0 x 3,0 mm) e acetonitrila-acetato de amônia 0,02 mol/L (80:20 v/v) como fase móvel. O método apresentou tempo total de corrida de 4,5 min e curva de calibração linear com concentrações entre 0,1-40 ng/mL (r > 0,9938). O limite de quantificação foi de 100 pg/mL. Os valores de precisão e exatidão foram obtidos por meio da análise das amostras de controle de qualidade. A análise de uma única amostra de plasma foi realizada em 4,5 minutos. A metodologia validada foi aplicada na determinação do perfil farmacocinético do nimodipino, comprimido de 30 mg administrado em 24 voluntários saudáveis. O método para quantificar nimodipino em plasma é adequado para aplicação em estudos farmacocinéticos, biodisponibilidade e bioequivalência em humanos.

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“…[4][5][6] Nimodipine has also been used in other cerebrovascular disorders, such as ischemic stroke [7][8][9][10][11] and multi-infarct dementia. 12,13 The mechanism of action has been attributed mainly to the inhibition of calcium influx through voltagegated L-type channels. However, recent studies have shown that therapeutic concentrations of nimodipine are able to inhibit adenosine transport in human red blood cells 14 and in human parietal cortex neurons.…”

mentioning

confidence: 99%

Nimodipine: Drug pharmacokinetics and plasma adenosine levels in patients affected by cerebral ischemia

Blardi

2002

Clin Pharma and Therapeutics

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Therapeutic Results with Nimodipine in Primary Degenerative Dementia and Multi-Infarct Dementia

Cited by 30 publications

References 7 publications

An efficacy and safety analysis of Exelon^® in Alzheimer’s disease patients with concurrent vascular risk factors

An efficacy and safety analysis of Exelon^® in Alzheimer’s disease patients with concurrent vascular risk factors

Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

Nimodipine: Drug pharmacokinetics and plasma adenosine levels in patients affected by cerebral ischemia

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Therapeutic Results with Nimodipine in Primary Degenerative Dementia and Multi-Infarct Dementia

Cited by 30 publications

References 7 publications

An efficacy and safety analysis of Exelon® in Alzheimer’s disease patients with concurrent vascular risk factors

An efficacy and safety analysis of Exelon® in Alzheimer’s disease patients with concurrent vascular risk factors

Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

Nimodipine: Drug pharmacokinetics and plasma adenosine levels in patients affected by cerebral ischemia

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Product

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An efficacy and safety analysis of Exelon^® in Alzheimer’s disease patients with concurrent vascular risk factors

An efficacy and safety analysis of Exelon^® in Alzheimer’s disease patients with concurrent vascular risk factors