Transfer of Nimodipine and Another Calcium Antagonist Across the Blood-Brain Barrier and Their Regional Distribution In Vivo

Kerckhoff, W. van den; Drewes, Lester R.

doi:10.1007/978-3-642-46658-8_24

Cited by 26 publications

(19 citation statements)

References 26 publications

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“…Due to its membrane permeability nimodipine readily crosses the blood-brain barrier [14]. In the CNS nimodipine exerts its action directly on neurons and on the cerebrovascular system [13,20].…”

Section: Discussionmentioning

confidence: 99%

“…Neuronal binding sites for dihydropyridines are most frequent in neuron-rich areas such as the hippocampus and the cerebral and cerebellar cortex [14]. Neuronal calcium homeostasis alters during ageing, tentatively because of an increased calcium influx through L-type calcium channels [16].…”

Section: Discussionmentioning

confidence: 99%

“…Nimodipine (Bay E 9736) is a calcium entry blocker of the 1,4-dihydropyridine type, which readily permeates the membranes of the blood brain barrier [14]. Therefore nimodipine preferentially acts via an improvement of cerebral microvascular function [13] and/or by a direct effect on the nervous system [20].…”

Section: Introductionmentioning

confidence: 99%

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Formation of cerebrovascular anomalies in the ageing rat is delayed by chronic nimodipine application

Jong¹,

Traber²,

Luiten³

1992

Mechanisms of Ageing and Development

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Formation of cerebrovascular anomalies in the ageing rat is delayed by chronic nimodipine application

Jong¹,

Traber²,

Luiten³

1992

Mechanisms of Ageing and Development

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“…Nimodipine is highly lipophilic (Mason et aI., 1990) and its volume of distribution in normal cerebral cortex has been reported to be 1.64 mllg (Van den Kerckhoff and Drewes, 1985). Using a small amino acid, we have shown that permeability of the BBB is slightly elevated after 4 h of ischemia (Hogan et aI., 1990), in agreement with other studies of BBB function in focal ischemia (Abe et aI., 1988;Hata shita and Hoff, 1988).…”

Section: Discussionmentioning

confidence: 99%

In vivo Binding of Nimodipine in the Brain: I. The Effect of Focal Cerebral Ischemia

Hakim

Hogan

1991

J Cereb Blood Flow Metab

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Summary:We report the regional variation in [3H]nimodipine binding in vivo during focal cerebral isch emia. After intravenous injection, 30 min of circulation of eH]nimodipine was sufficient to establish a secular equi librium of distribution in the brain. Rats sustained left middle cerebral and common carotid artery occlusions for 5 min, and 4, 24, and 48 h (n ?o 6 per group). They were decapitated 30 min after injection of 250 /l-Ci of eH]nimodipine and their brains were submitted to auto radiography. The concentrations of r3Hjnimodipine in plasma and brain structures, corrected for metabolism of nimodipine, were used to calculate the regional volumes Correlating these data with CBF and histologic determi nations performed in separate groups of rats, we conclude that eH]nimodipine binding increases earlier in the more severely ischemic structures than in those with more moderate reductions in perfusion. Furthermore, when binding declines in a region where it was previously in creased, infarction is likely. These studies afford new in sight into the concept of ischemic penumbra and suggest that this model may allow testing for therapeutic effec tiveness.

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“…Bmax is the number of VSCC sites available for binding and K'o is the binding affinity relative to the plasma nimodipine concentration. Because nimodipine freely crosses the blood-brain barrier (Van den Kerckhoff and Drewes, 1985), the concentrations of free nimodipine in plasma and tis sue will be equal. If ex is the solubility of nimodipine in plasma relative to water, then…”

Section: Theory the Modelmentioning

confidence: 99%

In vivo Binding of Nimodipine in the Brain: II. Binding Kinetics in Focal Cerebral Ischemia

Hogan

Gjedde

Hakim

1991

J Cereb Blood Flow Metab

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Summary:We report the binding characteristics of [3H]nimodipine to normal and ischemic brain in vivo, We used the 1,4-dihydropyridine, nimodipine, to label the L type voltage-sensitive calcium channel in focal cerebral ischemia after occlusion of both the middle cerebral and ipsilateral common carotid arteries in rats, Varying con centrations of [3H]nimodipine were infused 3,5 h after the onset of ischemia and circulated for 30 min before the brain was obtained for autoradiography and determina tion of regional nimodipine content. In separate sets of experiments, the metabolites of nimodipine were deter mined and the conditions for equilibrium of nimodipine

show abstract

Transfer of Nimodipine and Another Calcium Antagonist Across the Blood-Brain Barrier and Their Regional Distribution In Vivo

Cited by 26 publications

References 26 publications

Formation of cerebrovascular anomalies in the ageing rat is delayed by chronic nimodipine application

Formation of cerebrovascular anomalies in the ageing rat is delayed by chronic nimodipine application

In vivo Binding of Nimodipine in the Brain: I. The Effect of Focal Cerebral Ischemia

In vivo Binding of Nimodipine in the Brain: II. Binding Kinetics in Focal Cerebral Ischemia

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