Nimodipine

Scriabine, Alexander; Battye, Roy; Hoffmeister, F; Towart, R.; Garthoff, Bernward; Schlüter, G.; Rämsch, K.‐D.; Scherling, D.

doi:10.1111/j.1527-3466.1985.tb00479.x

Cited by 14 publications

(9 citation statements)

References 45 publications

(42 reference statements)

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“…Therapeutic concentrations of nimodipine are about 1 nm. (Plasma levels in clinical trials are 10-60 ng ml-' and approximately 2 % of this amount is free (Krol, Noe, Yeh & Raemsch, 1984;Scriabine et al 1985). Since the molecular weight of nimodipine is 418-5, the free concentration is 0 5-3 nm.…”

Section: Discussionmentioning

confidence: 99%

“…Lidocaine binds to Na channels in nerve, skeletal muscle and cardiac muscle with about the same affinity, and the binding affinity is modulated by channel gating. Na-channel block is very potent only in depolarized tissue, so that the drug preferentially affects ischaemic tissue (see Bean et al (1983) Scriabine et al (1985) for a review). The therapeutic efficacy has usually been attributed to vasodilatation of cerebral arteries, but in light of our studies direct effects on neuronal and/or neuroendocrine cells seem likely.…”

Section: Preferential Block Of Open Ca Channelsmentioning

confidence: 99%

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Nimodipine block of calcium channels in rat anterior pituitary cells.

Cohen

McCarthy

1987

The Journal of Physiology

158

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SUMMARY1. Ca channels were studied in the GH4C1 clonal cell line derived from rat anterior pituitary cells. The whole-cell variation of the patch-electrode voltage-clamp technique was used.2. Two types of Ca channels were found. One type ('slowly inactivating' channels) is insensitive to changes in holding potential, does not inactivate during test pulses lasting several seconds, and deactivates very quickly upon repolarization. For holding potentials <-40 mV, a second type of Ca channel is available for opening. This population ('transient' channels) differs from the first type in that it activates at more negative potentials, inactivates rapidly with either Ca or Ba as the charge carrier, deactivates about 10 times more slowly upon repolarization, and is less selective for Ba over Cs.3. Nimodipine preferentially blocks the slowly inactivating channels. Block of these channels is time-and voltage-dependent, such that block is maximized by long depolarizations.4

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Section: Discussionmentioning

confidence: 99%

Section: Preferential Block Of Open Ca Channelsmentioning

confidence: 99%

Nimodipine block of calcium channels in rat anterior pituitary cells.

Cohen

McCarthy

1987

The Journal of Physiology

158

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“…Clinical trials have shown beneficial effects of nimodipine in the treatment of subarachnoidal haemorrhage (Allen et aL, 1983;Ljunggren et aL, 1984), migraine (Gelmers, 1983;Meyer and Hardenberg, 1983) and stroke (Gelmers, 1984). Furthermore, the drug improves neurological recovery after complete cerebral ischemia in animals Steen et al, 1984; for review of the pharmacological effects of nimodipine see Scriabine et aL, 1985).…”

Section: Introductionmentioning

confidence: 97%

In vivo effects of the Ca2+-antagonist nimodipine on dopamine metabolism in mouse brain

Pileblad

Carlsson

1986

J. Neural Transmission

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The effects of the Ca2+-antagonist nimodipine on central dopamine (DA) neurons in mice were investigated in vivo. Nimodipine caused a dose-dependent decrease in the DA metabolite 3-methoxytyramine (3-MT) in striatum and the limbic region. If the brains were microwave radiated immediately after decapitation in order to minimize post-mortal accumulation of 3-MT, the effect of nimodipine was less pronounced and statistically not significant. Nimodipine markedly decreased the accumulation of 3-MT induced by pargyline, an inhibitor of monoamine oxidase, a phenomenon that was not attenuated by microwave radiation. Furthermore, whereas nimodipine had no effect on mouse motor activity when given alone it readily blocked the pargyline-induced increase in activity. The concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in striatum and the limbic region were also reduced by nimodipine as was the accumulation of 3,4-dihydroxyphenylalanine (DOPA) measured after inhibition of the aromatic amino acid decarboxylase by 3-hydroxybenzylhydrazine (NSD 1015). In addition, nimodipine caused decreased concentrations of DA and homovanillic acid (HVA) in the limbic region but not in striatum. Nimodipine caused an increase in the striatal concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA); these changes were not seen in the limbic region. In conclusion, nimodipine appears to reduce the release as well as the synthesis of DA in mouse brain. These effects are believed to be related to the Ca2+-antagonism of nimodipine.

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“…Similar results are obtained scaling for body surface area [16]. Furthermore, we estimated a human dose of intracranial nimodipine-PLGA might be in the vicinity of 760 mg because it is one-tenth of the human enteral dose over 21 days, given the approximately 10 % bioavailability of enteral nimodipine [17,18]. Nimodipine and placebo microparticles were suspended in low-viscosity hyaluronic acid buffer prior to intraventricular injection.…”

Section: Toxicity Studiesmentioning

confidence: 49%

A Site-Specific, Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage

et al. 2016

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Nimodipine is the only drug approved for use by the Food and Drug Administration for improving outcome after aneurysmal subarachnoid hemorrhage (SAH). It has less than optimal efficacy, causes dose-limiting hypotension in a substantial proportion of patients, and is administered enterally 6 times daily. We describe development of site-specific, sustainedrelease nimodipine microparticles that can be delivered once directly into the subarachnoid space or cerebral ventricles for potential improvement in outcome of patients with aneurysmal SAH. Eight injectable microparticle formulations of nimodipine in poly(DL-lactide-co-glycolide) (PLGA) polymers of varying composition were tested in vitro, and 1 was advanced into preclinical studies and clinical application. Intracisternal or intraventricular injection of nimodipine-PLGA microparticles in rats and beagles demonstrated dose-dependent, sustained concentrations of nimodipine in plasma and cerebrospinal fluid for up to 29 days with minimal toxicity in the brain or systemic tissues at doses <2 mg in rats and 51 mg in beagles, which would be equivalent of up to 612-1200 mg in humans, based on scaling relative to cerebrospinal fluid volumes. Efficacy was tested in the double-hemorrhage dog model of SAH. Nimodipine-PLGA microparticles significantly attenuated angiographic vasospasm. This therapeutic approach shows promise for improving outcome after SAH and may have broader applicability for similar diseases that are confined to body cavities or spaces, are self-limited, and lack effective treatments.

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Nimodipine

Abstract: Nimodipine (BAY e 9736) is a Ca2+-channel antagonist of a dihydropyridine type. Its chemical name is 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl-1-methylethyl ester ( Fig.

Cited by 14 publications

References 45 publications

Nimodipine block of calcium channels in rat anterior pituitary cells.

Nimodipine block of calcium channels in rat anterior pituitary cells.

In vivo effects of the Ca2+-antagonist nimodipine on dopamine metabolism in mouse brain

A Site-Specific, Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage

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