Document Detail

The connexin 36 blockers quinine, quinidine and mefloquine inhibit cortical spreading depression in a rat neocortical slice model in vitro.
MedLine Citation:
PMID:  17113924     Owner:  NLM     Status:  MEDLINE    
A protocol for inducing cortical spreading depression (SD) on rat neocortical slices in vitro, upon local application of calibrated approximately nl drops of KCl, 3M was used to elicit SD events, recorded at two different points on the slice. This in vitro model was validated by the inhibition of SD episodes by the NMDA antagonist MK-801 (20 microM), the reference SD blocker. Quinine, its stereoisomer quinidine, and mefloquine consistently inhibited the SD episodes. Quinine and quinidine, 100 and 200 microM reduced the duration, while mefloquine, 100 and 200 microM reduced the amplitude of SD events, all in a concentration-dependent manner. These compounds have been reported to block gap junctions, specifically the neuronal connexin (Cx) 36, but they also exert other cellular effects. While further investigation is warranted to settle whether SD inhibition in vitro by quinine, quinidine and mefloquine reflects an involvement of neuronal Cx36 channels in SD generation/propagation, these results bear potential drug-discovery relevance for the migraine with aura.
Doru Georg Margineanu; Henrik Klitgaard
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Publication Detail:
Type:  Journal Article     Date:  2006-08-11
Journal Detail:
Title:  Brain research bulletin     Volume:  71     ISSN:  0361-9230     ISO Abbreviation:  Brain Res. Bull.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-20     Completed Date:  2007-02-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7605818     Medline TA:  Brain Res Bull     Country:  United States    
Other Details:
Languages:  eng     Pagination:  23-8     Citation Subset:  IM    
UCB S.A., CNS Research, B-1420 Braine-l'Alleud, Belgium.
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MeSH Terms
Cell Communication / drug effects,  physiology*
Connexins / antagonists & inhibitors,  metabolism*
Cortical Spreading Depression / drug effects,  physiology*
Dose-Response Relationship, Drug
Gap Junctions / drug effects,  metabolism*
Mefloquine / pharmacology
Membrane Potentials / drug effects,  physiology
Models, Neurological
Neocortex / drug effects,  metabolism,  physiopathology*
Organ Culture Techniques
Potassium Channel Blockers / pharmacology
Quinidine / pharmacology
Quinine / pharmacology
Rats, Sprague-Dawley
Reg. No./Substance:
0/Connexins; 0/Potassium Channel Blockers; 0/connexin 36; 130-95-0/Quinine; 53230-10-7/Mefloquine; 56-54-2/Quinidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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