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Literature DB >> 12709303

Neuroprotective effects of NS-7, voltage-gated Na+/Ca2+ channel blocker in a rodent model of transient focal ischaemia.

Monika Sopala¹, Wojciech Danysz, Guenter Quack.

Abstract

The aim of the present study was to characterize neuroprotective activity of NS- 7, a mixed voltage-gated sodium and calcium channel blocker in a model of transient focal ischaemia in rats. Ischaemia was induced by a 75 min reversible occlusion of middle cerebral artery (MCAo) using a nylon filament. NS-7 (0.5 mg/kg i.v.) or 0.9% NaCl (1 ml/kg i.v.) were infused over 3 min. starting 30 min after the MCAo. Infarct analysis was performed 72 h after ischaemia. Application of NS- 7 produced significant protection seen in neurological tests and diminished brain damage by 37% in total infarct (17.7+/- 3.0% vs. 27.9 +/- 3.2% control; [p < 0.01]; t-test), 47.8% in cortical infarct size by (8.5 +/- 2.4% vs. 16.2 +/- 2.4% control; [p < 0.01]), and by 21.5% in striatal infarction (9.2 +/- 0.8% vs. 11.7 +/- 0.9% control; [p < 0.05]). The results indicate that NS- 7 has potential for neuroprotection against transient ischaemic insult.

Entities: Chemical Disease Species

Year: 2002 PMID： 12709303 DOI： 10.1080/1029842021000045462

Source DB: PubMed Journal: Neurotox Res ISSN： 1029-8428 Impact factor: 3.911

36 in total

1. Blockade by NS-7, a neuroprotective compound, of both L-type and P/Q-type Ca2+ channels involving depolarization-stimulated nitric oxide synthase activity in primary neuronal culture.

Authors: M Oka; Y Itoh; Y Ukai; K Kimura
Journal: J Neurochem Date: 1999-03 Impact factor: 5.372

2. Inhibition of depolarization-induced nitric oxide synthase activation by NS-7, a phenylpyrimidine derivative, in primary neuronal culture.

Authors: S Tatsumi; Y Itoh; F H Ma; H Higashira; Y Ukai; Y Yoshikuni; K Kimura
Journal: J Neurochem Date: 1998-01 Impact factor: 5.372

3. Behavioral effects and anticonvulsant efficacies of low-affinity, uncompetitive NMDA antagonists in mice.

Authors: B Geter-Douglass; J M Witkin
Journal: Psychopharmacology (Berl) Date: 1999-10 Impact factor: 4.530

4. MRZ 2/579, a novel uncompetitive N-methyl-D-aspartate antagonist, reduces infarct volume and brain swelling and improves neurological deficit after focal cerebral ischemia in rats.

Authors: Y Liu; L Belayev; W Zhao; R Busto; M D Ginsberg
Journal: Brain Res Date: 2000-04-17 Impact factor: 3.252

5. Development of tissue damage, inflammation and resolution following stroke: an immunohistochemical and quantitative planimetric study.

Authors: R K Clark; E V Lee; C J Fish; R F White; W J Price; Z L Jonak; G Z Feuerstein; F C Barone
Journal: Brain Res Bull Date: 1993 Impact factor: 4.077

6. Neuronal protective effects of calcium antagonists in cerebral ischemia.

Authors: A Rami; J Krieglstein
Journal: Life Sci Date: 1994 Impact factor: 5.037

7. A selective N-type Ca(2+)-channel blocker prevents CA1 injury 24 h following severe forebrain ischemia and reduces infarction following focal ischemia.

Authors: A M Buchan; S Z Gertler; H Li; D Xue; Z G Huang; K E Chaundy; K Barnes; H J Lesiuk
Journal: J Cereb Blood Flow Metab Date: 1994-11 Impact factor: 6.200

2. Decreasing the infusion rate reduces the proarrhythmic risk of NS-7: confirming the relevance of short-term variability of repolarisation in predicting drug-induced torsades de pointes.

Authors: Elke Detre; Morten B Thomsen; Jet D Beekman; Karl-Uwe Petersen; Marc A Vos
Journal: Br J Pharmacol Date: 2005-06 Impact factor: 8.739

2 in total

Neuroprotective effects of NS-7, voltage-gated Na+/Ca2+ channel blocker in a rodent model of transient focal ischaemia.

1. Blockade by NS-7, a neuroprotective compound, of both L-type and P/Q-type Ca2+ channels involving depolarization-stimulated nitric oxide synthase activity in primary neuronal culture.

2. Inhibition of depolarization-induced nitric oxide synthase activation by NS-7, a phenylpyrimidine derivative, in primary neuronal culture.

3. Behavioral effects and anticonvulsant efficacies of low-affinity, uncompetitive NMDA antagonists in mice.

4. MRZ 2/579, a novel uncompetitive N-methyl-D-aspartate antagonist, reduces infarct volume and brain swelling and improves neurological deficit after focal cerebral ischemia in rats.

5. Development of tissue damage, inflammation and resolution following stroke: an immunohistochemical and quantitative planimetric study.

6. Neuronal protective effects of calcium antagonists in cerebral ischemia.

7. A selective N-type Ca(2+)-channel blocker prevents CA1 injury 24 h following severe forebrain ischemia and reduces infarction following focal ischemia.

8. Reversible middle cerebral artery occlusion without craniectomy in rats.

Review 9. [The N-methyl-D-aspartate receptor complex. Various sites of regulation and clinical consequences].

Review 10. Neuroprotective use-dependent blockers of Na+ and Ca2+ channels controlling presynaptic release of glutamate.

1. Neuroprotective effect of the novel Na+/Ca2+ channel blocker NS-7 on rat retinal ganglion cells.

2. Decreasing the infusion rate reduces the proarrhythmic risk of NS-7: confirming the relevance of short-term variability of repolarisation in predicting drug-induced torsades de pointes.