NIMODIPINE

The flux of calcium forms an important intracellular messenger system. The bcl-2 oncoprotein is thought to make cells resistant to a variety of insults, including cytotoxic drugs, by the suppression of apoptosis, which appears to involve the repartitioning of intracellular calcium. Three drugs that affect calcium pathways and may influence this repartitioning, i.e. dantrolene, azumolene (a water-soluble dantrolene analogue) and nimodipine, were studied in cell culture, using both a transformed follicle centre lymphoma cell line and primary culture of lymphoma cells in vitro in a manner that resulted in a growth pattern closely resembling that of the malignancy in vivo. Dantrolene and azumolene were potent inducers of cell death in both systems reducing the viable cell count by 70-90% in comparison with normal controls. Nimodipine, in comparison, appeared to have no significant effect. These results obtained in an in vitro setting suggest that further evaluation of dantrolene and azu...

To explore the contribution of renal failure to nimodipine overall pharmacokinetic variability after single and multiple oral dosing and to develop a population pharmacokinetic model by means of the nonparametric expectation maximization (NPEM2) algorithm based on sampled individual drug concentrations close to the estimated patients' C(SS)avs (NPEM2-C(SS)av). 24 hypertensive patients with normal and reduced renal function, without clinical and laboratory data for hepatic dysfunction, were enrolled in the study and their nimodipine plasma levels were analyzed by means of a parametric and nonparametric population pharmacokinetic modeling using a maximum a posteriori Bayesian (MAPB) estimator in an iterative two-stage Bayesian population modeling program and NPEM2-algorithm. Comparison of parameter dispersion revealed higher variability of nimodipine disposition after the first dose than at steady-state except for apparent volume of distribution at steady-state, V(SS)/F, whose var...

Bipolar disorder (BD) is characterized by periods of abnormally elevated mood (mania) that cycle with abnormally lowered mood (depression). Multiple structural, metabolic, and biochemical abnormalities are evident in the brain's cortex, subcortex, and deeper regions. This disorder is highly genetically conditioned but also highly susceptible to environmental stressors: prenatal or perinatal insults, childhood sexual or physical abuse, challenging life events, substance abuse, and other toxic chemical exposures. Its high morbidity, lost productivity, and suicide risk place a great toll on society. Since World War II, BD has been steadily worsening with earlier age of onset, greater intensity of symptoms, and development of drug resistance. Incidence in children is rising and misdiagnosis is common. Disciplined management of the many risk factors is essential, including cognitive psychotherapy and support from family and community. Lithium has been the foundational treatment, foll...

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 p...

It has been shown recently that extinction of conditional fear does not depend acutely on NMDA-type glutamate receptors, although other evidence has led to the hypothesis that L-type voltage-gated calcium channels (LVGCCs) play a role in conditional fear. We therefore tested the role of LVGCCs in the acquisition, expression, and extinction of conditional fear of cue and context in mice. Using systemic injections of two LVGCC inhibitors, nifedipine and nimodipine, which both effectively cross the blood-brain barrier, we show that LVGCCs are essential for the extinction, but not for the acquisition or expression, of conditional fear in mice.

Developmental changes in the signaling properties of NMDA receptors have been proposed to underlie the loss of plasticity that accompanies brain maturation. Calcium influx through postsynaptic NMDA receptors can stimulate neuronal gene expression via signaling pathways such as ...

Rats repeatedly intoxicated with alcohol (ethanol, three times daily) over a 4-day period display neuronal degeneration in the dentate gyrus; entorhinal, piriform, insular, orbital, and perirhinal cortices; and in the olfactory nerve fibers and terminals in the olfactory bulb. Postulating a ...

1. Current through Ca2+ channels was studied in acutely isolated guinea-pig pyramidal neurones from the CA3 region of the hippocampus. Both the whole-cell and single-channel patch-clamp configuration were used. 2. Both whole-cell and single-channel currents displayed holding potential sensitivity indicative of two high-threshold currents similar to L- and N-type Ca2+ currents. 3. A low-threshold whole-cell current, similar to T-type current seen in dorsal root ganglion (DRG) neurones, activated at -60 to -50 mV and was blocked by nickel (100 microM) and amiloride (500 microM). Exposure to 50 microM-cadmium left a fraction of the T-type current intact but blocked N- and L-type current. This T-like component needed extremely negative holding potentials to be completely reprimed. 4. Whole-cell N-type Ca2+ channel current was blocked by omega-conotoxin (1 microM). From a holding potential of -90 mV, omega-conotoxin decreased the peak whole-cell current by 33%. 5. A slowly inactivating h...

Cerebral vasospasm remains a major problem in patients recovering from aneurysmal subarachnoid hemorrhage despite advances in medical, surgical, and endovascular care. Our purpose was to assess the efficacy of intra-arterial nimodipine, a calcium-channel blocker acting mainly on cerebral vessels, in preventing delayed neurologic deficits in patients with symptomatic vasospasm. Clinical charts of 25 consecutively treated patients were retrospectively reviewed. A multifactorial decision tree was used to determine the indication for angiography and subsequent endovascular treatment. Nimodipine was infused intra-arterially via a diagnostic catheter in the internal carotid artery or vertebral artery at a rate of 0.1 mg/min. Angiographic vasospasm before endovascular treatment, immediate vessel caliber modifications, and short- and long-term clinical efficacy of the procedure were assessed. Thirty procedures were performed in 25 patients. Clinical improvement was observed in 19 (76%), 16 ...

We used the [14C]iodoantipyrine autoradiography technique to study the effect of pretreatment with the calcium antagonist nimodipine on local cerebral blood flow (1CBF) in rats that underwent middle cerebral artery (MCA) occlusion. In untreated control animals there were profound localized reductions in 1CBF 30 minutes after MCA occlusion. These were most pronounced in neocortical areas and in the caudate nucleus ipsilateral to the MCA occlusion. In animals pretreated with nimodipine (1 μg · kg−1 · min−1 for 30 minutes before and 30 minutes after MCA occlusion), the ipsilateral decrease in 1CBF in cortical regions was significantly less than that in control animals. The drug did not appear to alter 1CBF in the ipsilateral caudate nucleus. Neuropathological quantification of the ischemic damage present 3 hours after occlusion showed thai: nimodipine pretreatment reduced the volume and extent of cellular damage in the periphery but not in the core of the lesion.

Summary— The neuroprotective role of nimodipine was tested in kainic acid (50 and 100 μM) induced neurotoxicity in cerebellar granular cell cultures of 4 to 7 day-old rat pups. Nimodipine was applied in 50, 100 and 200 μM concentrations. Kainate, in either dose, induced cerebellar granular cell death in respect to controls and the results were statistically significant (P = 0.000 for both doses). However, kainic acid in 100 μM concentration led to higher rates of cell death than 50 μM (P = 0.017). The neuroprotective role of nimodipine in kainate induced neurotoxicity was dose dependent. Kainate toxicity in 50 μM concentration was blocked by 50 and 100 μM nimodipine concentrations (P = 0.006 and P = 0.002, respectively) while 200 μM nimodipine was found ineffective. The most effective nimodipine dose for 100 μM kainic acid neurotoxicity was 200 μM (P = 0.000) while 50 and 100 μM concentrations of nimodipine were found ineffective. In this study, we have proven the dose-dependent neuroprotective role of nimodipine in kainate induced neurotoxicity in cerebellar granular cell cultures of rat pups.