Beneficial effect of nimodipine on metabolic and functional disturbances in rabbit hippocampus following complete cerebral ischemia.

Łazarewicz, Jerzy W.; Pluta, Ryszard; Salińska, Elżbieta; Puka, M

doi:10.1161/01.str.20.1.70

Cited by 37 publications

(11 citation statements)

References 34 publications

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“…Blockers of the L-type voltage-sensitive calcium channel in ischemia have recently been reviewed. 36 In global cerebral ischemia, studies have yielded both positive 37 and negative 9 results. Similar to the pattern of results emerging with MK-801, investigations using nimodipine are more decidedly positive in focal ischemia than in global ischemia.…”

Section: Discussionmentioning

confidence: 99%

Combination therapy with nimodipine and dizocilpine in a rat model of transient forebrain ischemia.

Rod

Auer

1992

Stroke

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Background and Purpose:We explored the effectiveness of dual blockade of calcium channels in preventing ischemic necrosis in a rat model of transient forebrain ischemia.Methods: To assess all the major brain regions, the entire brain was subseriallv sectioned and examined histologically 1 week after ischemia in 44 male Wistar rats. Brain temperature was monitored and controlled to avoid hypothermia or intergroup temperature differences at the time drugs were administered. All regimens were begun 20 minutes after the ischemia. Treated animals received either the L-type calcium channel blocker nimodipine (0.25 /ig/minx24-hour i.v. infusion), the noncompetitive A'-raethyl-D-aspartate receptor antagonist MK-801 (dizocilpine; 5 mg/kg i.v.), or both regimens in combination.Results: In the neocortex (p<0.05) and striatum (p<0.05), only double-treated animals showed a statistically significant reduction in neuronal necrosis. Dual therapy eliminated neuronal necrosis in the caudate nucleus entirely. In the septa I (densely ischemic) hippocampus, protection was weak and inconsistent (0.012

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Section: Discussionmentioning

confidence: 99%

Combination therapy with nimodipine and dizocilpine in a rat model of transient forebrain ischemia.

Rod

Auer

1992

Stroke

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“…Mohamed et al, 1984), other studies have found this compound to have little influence on cerebral blood flow. This apparent absence of cerebral vasodilatation has raised the possibility that the beneficial effect of nimodipine iificantly after on the outcome of subarachnoid haemorrhage (Pickard et al, 1989) might be due to influences on metabolic processes (Berger & Hakim, 1988) and/or on cellular calcium fluxes dipine vehicle (Lazarewicz et al, 1989) following activation of excitotoxic t this was not amino acid-mediated mechanisms. If such a mechanism does re no changes contribute to the therapeutic influence of nimodipine (see istrated).…”

Section: Discussionmentioning

confidence: 99%

Synergistic internal carotid vasodilator effects of human α‐calcitonin gene‐related peptide and nimodipine in conscious rats

Gardiner

Compton

Bennett

et al. 1990

British J Pharmacology

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1 In a first series of experiments, male Long Evans rats were chronically instrumented for the measurement of internal carotid blood flow and systemic arterial blood pressure; cardiovascular changes were assessed during and after 30min infusions of human a-calcitonin gene-related peptide (CGRP) (0.06 and 0.6 nmol h 1), or nimodipine (60 and 600 nmol hV ) or human a-CGRP plus nimodipine. The effects of human a-CGRP or nimodipine on internal carotid vasoconstriction induced by endothelin-1 were also measured.2 Human a-CGRP (0.06nmolh-') caused a small (+15%), transient increase in internal carotid blood flow and a tachycardia (+ 33 beats min-1), but no change in mean blood pressure. Nimodipine (60 nmol h-) caused a brief internal carotid hyperaemia (+16%) but no changes in blood pressure or heart rate. However, concurrent administration of human a-CGRP (0.06nmolh-1) and nimodipine (60nmolh-1) caused a sustained increase in internal carotid blood flow (+40%) unaccompanied by significant changes in heart rate or blood pressure.3 Human a-CGRP at a dose of 0.6 nmol h-' or nimodipine at a dose of 600 nmol h-1 caused substantial reductions in internal carotid vascular resistance (-43 and -40%, respectively); concurrent administration of these doses did not have an additive vasodilator effect. 4 Infusion of endothelin-1 (1.2nmolhV1) for 20min caused incremental constriction of the internal carotid vascular bed; human a-CGRP infusion (0.6 and 6.0nmolh-1) begun tOmin after the onset of endothelin-1 infusion reversed this effect (dose-dependently); nimodipine (600nmolh-1) also caused a substantial attenuation of the effects of endothelin-1. 5 In a second series of experiments the haemodynamic effects of human a-CGRP and/or nimodipine were assessed in rats chronically instrumented for the measurement of renal, superior mesenteric and hindquarters blood flow together with systemic arterial blood pressure.6 Administration of human a-CGRP (0.06 nmol h-') alone or in conjuction with nimodipine (60nmolh-1) had no significant effects on renal or superior mesenteric vascular resistances, although there was a slight hindquarters vasodilatation. Human a-CGRP at a dose of 0.6 nmol -1 caused hypotension, tachycardia and reductions in renal and superior mesenteric blood flows, together with a marked (+31% maximum) hindquarters hyperaemia. Nimodipine at a dose of 600 nmol h-1 caused hypotension, tachycardia and a reduction (-34%) in renal blood flow; mesenteric blood flow was unchanged and there was an increase in hindquarters flow (+ 59%). 7 Concurrent administration of human a-CGRP (0.6 nmol h 1) and nimodipine (600 nmol h') did not have an additive hypotensive effect or an enhanced hindquarters hyperaemic effect, but was associated with a marked impairment of renal blood flow (-48%). 8 The present results indicate that concurrent administration of low doses of human a-CGRP and nimodipine might be particularly helpful in the acute treatment of patients with cerebral vasospasm and impaired renal perfusion, since this intervention imp...

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“…Study in clarity and stability of the MMs was performed to evaluate the safety of the IVM-SPC-SDC-MMs for clinical use (Lazarewicz et al, 1989). As is shown in the results, when the commercially available IVM injection was diluted to a certain concentration, due to the reduction of the organic solvent proportion, IVM crystal appeared immediately, which is disadvantageous in clinical application.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneously injected ivermectin-loaded mixed micelles: formulation, pharmacokinetics and local irritation study

Dong

Lian

et al. 2014

Drug Delivery

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Clinical application of ivermectin (IVM) is limited by several unfavorable properties, induced by its insolubility in water. Slight differences in formulation may change the plasma pharmacokinetics and efficacy. In this study, an IVM-loaded Soy phosphatidylcholine-sodium deoxycholate mixed micelles (IVM-SPC-SDC-MMs) were developed to improve its aqueous solubility, aiming to make it more applicable for clinical use. First, IVM-SPC-SDC-MMs were prepared using the co-precipitation method. After formulation optimization, the particle size was 9.46 ± 0.16 nm according to dynamic light scattering. The water solubility of IVM in SPC-SDC-MMs (4.79 ± 0.02 mg/mL) was improved by 1200-fold, comparing with free IVM (0.004 mg/mL). After subcutaneous administration, the pharmacokinetic study showed that IVM-SPC-SDC-MMs and commercially available IVM injection were bioequivalent. Also, the local irritation study confirmed that IVM-SPC-SDC-MMs reduced side reactions of the commercially available IVM injection. These results indicated that IVM-SPC-SDC-MMs represented a promising new drug formulation suitable for subcutaneous delivery of IVM.

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Beneficial effect of nimodipine on metabolic and functional disturbances in rabbit hippocampus following complete cerebral ischemia.

Cited by 37 publications

References 34 publications

Combination therapy with nimodipine and dizocilpine in a rat model of transient forebrain ischemia.

Combination therapy with nimodipine and dizocilpine in a rat model of transient forebrain ischemia.

Synergistic internal carotid vasodilator effects of human α‐calcitonin gene‐related peptide and nimodipine in conscious rats

Subcutaneously injected ivermectin-loaded mixed micelles: formulation, pharmacokinetics and local irritation study

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