Source:http://linkedlifedata.com/resource/pubmed/id/20547167
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2010-9-27
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| pubmed:abstractText |
Essential tremor is a common disorder that lacks molecular targets for therapeutic development. T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in essential tremor. We therefore tested whether compounds that antagonize T-type calcium channel currents suppress tremor in two mouse models that possess an essential tremor-like pharmacological response profile. Tremor was measured using digitized spectral motion power analysis with harmaline-induced tremor and in the GABA(A) receptor ?1 subunit-null model. Mice were given ethosuximide, zonisamide, the neuroactive steroid (3?,5?,17?)-17-hydroxyestrane-3-carbonitrile (ECN), the 3,4-dihydroquinazoline derivative KYS05064, the mibefradil derivative NNC 55-0396, or vehicle. In non-sedating doses, each compound reduced harmaline-induced tremor by at least 50% (range of maximal suppression: 53-81%), and in the GABA(A) ?1-null model by at least 70% (range 70-93%). Because the T-type calcium channel Cav3.1 is the dominant subtype expressed in the inferior olive, we assessed the tremor response of Cav3.1-deficient mice to harmaline, and found that null and heterozygote mice exhibit as much tremor as wild-type mice. In addition, ECN and NNC 55-0396 suppressed harmaline tremor as well in Cav3.1-null mice as in wild-type mice. The finding that five T-type calcium antagonists suppress tremor in two animal tremor models suggests that T-type calcium channels may be an appropriate target for essential tremor therapy development. It is uncertain whether medications developed to block only the Cav3.1 subtype would exhibit efficacy.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/(1S,2S)-2-(2-(N-((3-benzimidazol-2-y...,
http://linkedlifedata.com/resource/pubmed/chemical/17-hydroxyestrane-3-carbonitrile,
http://linkedlifedata.com/resource/pubmed/chemical/Benzimidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, T-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclopropanes,
http://linkedlifedata.com/resource/pubmed/chemical/Estranes,
http://linkedlifedata.com/resource/pubmed/chemical/Ethosuximide,
http://linkedlifedata.com/resource/pubmed/chemical/Harmaline,
http://linkedlifedata.com/resource/pubmed/chemical/Isoxazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-A,
http://linkedlifedata.com/resource/pubmed/chemical/zonisamide
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
1873-7064
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ltd. All rights reserved.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
59
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
380-7
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| pubmed:dateRevised |
2011-2-25
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| pubmed:meshHeading |
pubmed-meshheading:20547167-Analysis of Variance,
pubmed-meshheading:20547167-Animals,
pubmed-meshheading:20547167-Benzimidazoles,
pubmed-meshheading:20547167-Calcium Channel Blockers,
pubmed-meshheading:20547167-Calcium Channels, T-Type,
pubmed-meshheading:20547167-Cyclopropanes,
pubmed-meshheading:20547167-Disease Models, Animal,
pubmed-meshheading:20547167-Essential Tremor,
pubmed-meshheading:20547167-Estranes,
pubmed-meshheading:20547167-Ethosuximide,
pubmed-meshheading:20547167-Harmaline,
pubmed-meshheading:20547167-Isoxazoles,
pubmed-meshheading:20547167-Male,
pubmed-meshheading:20547167-Mice,
pubmed-meshheading:20547167-Mice, Inbred ICR,
pubmed-meshheading:20547167-Mice, Knockout,
pubmed-meshheading:20547167-Naphthalenes,
pubmed-meshheading:20547167-Nitriles,
pubmed-meshheading:20547167-Receptors, GABA-A
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| pubmed:year |
2010
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| pubmed:articleTitle |
T-type calcium channel antagonists suppress tremor in two mouse models of essential tremor.
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| pubmed:affiliation |
Neurology Service (W127), Veterans Affairs Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, Los Angeles, CA 90073, USA. charles.handforth@va.gov
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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