Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride.
Acid Sensing Ion Channels
/ genetics
Amiloride
/ adverse effects
Animals
Brain Ischemia
/ drug therapy
Calcium Channels, L-Type
/ drug effects
Cells, Cultured
Glucose
/ metabolism
Hippocampus
/ drug effects
Humans
Mice
Neurons
/ drug effects
Neuroprotective Agents
/ adverse effects
Nimodipine
/ adverse effects
Oxygen
/ metabolism
acid-sensing ion channels
amiloride
neural injury
neuroprotection
nimodipine
oxygen-glucose deprivation
subarachnoid haemorrhage
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
24 Nov 2020
24 Nov 2020
Historique:
received:
07
11
2020
revised:
19
11
2020
accepted:
20
11
2020
entrez:
1
12
2020
pubmed:
2
12
2020
medline:
6
3
2021
Statut:
epublish
Résumé
Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs-nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)-might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (
Identifiants
pubmed: 33255506
pii: ijms21238921
doi: 10.3390/ijms21238921
pmc: PMC7727815
pii:
doi:
Substances chimiques
ASIC1 protein, mouse
0
Acid Sensing Ion Channels
0
Calcium Channels, L-Type
0
Neuroprotective Agents
0
Nimodipine
57WA9QZ5WH
Amiloride
7DZO8EB0Z3
Glucose
IY9XDZ35W2
Oxygen
S88TT14065
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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