Depolarization‐Induced Presynaptic Calcium Accumulation May Occur by an N‐Type Channel That Is Blocked by Flunarizine

Cohan, Stanley; Chen, Mei; Redmond, David J.; Wilson, Dahlia

doi:10.1111/j.1749-6632.1991.tb36508.x

Cited by 7 publications

(3 citation statements)

References 8 publications

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“…Calcium overload is an important potential mechanism of postischemic neuronal damage,'-4 and increased intraneuronal calcium has been observed ultrastructurally immediately after cessation of global cerebral ischemia. 7 Flunarizine inhibits calcium conductance through T-and L-type voltage-regulated channels in cardiac muscle, 17 inhibits calcium conductance through T-type channels in rat hypothalamic neurons, 18 blocks presynaptic calcium uptake after sustained in vitro depolarization, 19 and also delays anoxia-induced neuronal depolarization. 20 Flunarizine acts as a calcium antagonist, but probably has other modes of action as well, particularly as a sodium antagonist.…”

Section: Discussionmentioning

confidence: 99%

Effect of flunarizine on electroencephalogram recovery and brain temperature in gerbils after brain ischemia.

Cohan

Redmond

Chen

1992

Stroke

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Background and Purpose: This study was designed to determine whether flunarizine enhances the rate of brain recovery as measured by electroencephalography after cerebral ischemia and whether these effects are attributable to changes in brain temperature.Methods: Male gerbils (n=81) were treated with either 10 mg/kg flunarizine or its vehicle, /3-cyclodextrin, intraperitoneally, 60 minutes before bilateral carotid occlusion of either 4 or 6 minutes' duration. The electroencephalogram was continuously recorded in the preischemic, ischemic, and postischemic stages of the experiment and rated for the time necessary for the return of 4-6, 7-10, and 11-15 Hz activity. In a second set of experiments, intracerebral temperature was monitored for 60 minutes before ischemia, during 10 minutes of carotid occlusion, and for 60 minutes after ischemia.Results: Flunarizine pretreatment resulted in significantly more rapid return of electroencephalographic activity in each of the three frequency categories monitored when compared with those animals pretreated with vehicle alone (p<0.001). Flunarizine had no effect on brain temperature before, during, or up to 60 minutes after termination of ischemia.Conclusions: Flunarizine, which has been of efficacy in reducing neuronal death, mortality, and functional impairment when administered after ischemic insults, may have prophylactic value in accelerating brain recovery from ischemia, but does not have this effect as a result of altered brain temperature. (Stroke 1992;23:229-233)

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Section: Discussionmentioning

confidence: 99%

Effect of flunarizine on electroencephalogram recovery and brain temperature in gerbils after brain ischemia.

Cohan

Redmond

Chen

1992

Stroke

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“…As an example, Chart 1 reports some L-type classical antagonists that have also shown remarkable N-type antagonism: (S)-emopamil, 19 cilnidipine, 20 flunarizine. 21 More interestingly, structural motifs of L-type antagonists can be found in the new molecules designed as N-type antagonists such as compounds A 22 and B 23 shown in Chart 1. These results seem to suggest that it is possible to obtain N-type calcium channel antagonists by molecular manipulation of the structure of L-type antagonists and on this basis, we have designed the series of compounds shown in Chart 2.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, during the past decade, it was found that the classic L-type antagonists are not that specific, as a few of them show some action also on other types of calcium channels, namely the N-type. As an example, Chart reports some L-type classical antagonists that have also shown remarkable N-type antagonism: ( S )-emopamil, cilnidipine, flunarizine . More interestingly, structural motifs of L-type antagonists can be found in the new molecules designed as N-type antagonists such as compounds A and B shown in Chart .…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Preliminary Pharmacological Evaluation of 4-Aminopiperidine Derivatives as N-Type Calcium Channel Blockers Active on Pain and Neuropathic Pain

et al. 2004

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Several compounds with a 4-aminopiperidine scaffold decorated on both nitrogen atoms by alkyl or acyl moieties containing the structural motifs of verapamil and of flunarizine, as well as those that are more frequent in known N-type calcium channel antagonists, have been synthesized. Antinociceptive activity on the mouse hot-plate test was used to select molecules to be submitted to further studies. Active compounds were tested in vitro on a PC12 rat pheochromocytoma clonal cell line, to evaluate their action on N-type calcium channels, and on a rat model of neuropathic pain. Two compounds that show N-type calcium channel antagonism and are endowed with potent action on pain and neuropathic pain (3 and 18) have been selected for further studies.

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Studies on Synaptosomes: New Insights on Calcium Antagonists

Cohan

Getz

Chen

1993

Calcium Antagonists

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Depolarization‐Induced Presynaptic Calcium Accumulation May Occur by an N‐Type Channel That Is Blocked by Flunarizine

Cited by 7 publications

References 8 publications

Effect of flunarizine on electroencephalogram recovery and brain temperature in gerbils after brain ischemia.

Effect of flunarizine on electroencephalogram recovery and brain temperature in gerbils after brain ischemia.

Design, Synthesis, and Preliminary Pharmacological Evaluation of 4-Aminopiperidine Derivatives as N-Type Calcium Channel Blockers Active on Pain and Neuropathic Pain

Studies on Synaptosomes: New Insights on Calcium Antagonists

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