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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1990-6-27
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pubmed:abstractText |
Hypothermia induced by either clozapine or clonidine in mice was blocked by the alpha 2-adrenergic antagonists yohimbine, idazoxan, CH-38083, SKF 86466, and L-657,743. These effects were dose related, and the ID50 values for inhibition of clozapine- or clonidine-induced hypothermia were fairly comparable. The order of potency for blocking clonidine-induced hypothermia was: L-657,743 greater than CH-38083 greater than yohimbine greater than idazoxan greater than SKF 86466. A very similar blockade hierarchy for clozapine-induced hypothermia was observed, with the order of the two most effective compounds being reversed. Hypothermia induced by either compound was not blocked by the peripherally-acting, selective alpha 2-adrenergic antagonist, L-659,066, indicating that blockade by the other compounds occurred centrally. The centrally-acting, alpha 1-adrenergic agonists St 587, cirazoline, and SKF 89748 were very effective in blocking the response to clozapine, but ineffective in antagonizing clonidine-induced hypothermia. The ED50 values for the blockade of this response to clozapine, however, did not correlate with their reported potencies in stimulating either peripheral or central alpha 1-adrenergic receptors. This indicates that clozapine-induced hypothermia in mice is not a suitable model for evaluating the properties of central alpha 1-adrenergic compounds. Moreover, since the clonidine-induced hypothermia is not influenced by alpha 1-adrenergic agonists, this paradigm is preferable to clozapine-induced hypothermia in the assessment of alpha 2-adrenergic antagonism The ability of alpha 2-adrenergic antagonists to block clozapine-induced hypothermia may result from the central overflow of norepinephrine, which is known to be brought about by this group of compounds.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Clonidine,
http://linkedlifedata.com/resource/pubmed/chemical/Clozapine,
http://linkedlifedata.com/resource/pubmed/chemical/Dibenzazepines
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pubmed:status |
MEDLINE
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pubmed:issn |
0033-3158
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
67-72
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:1971449-Adrenergic alpha-Agonists,
pubmed-meshheading:1971449-Adrenergic alpha-Antagonists,
pubmed-meshheading:1971449-Animals,
pubmed-meshheading:1971449-Body Temperature,
pubmed-meshheading:1971449-Clonidine,
pubmed-meshheading:1971449-Clozapine,
pubmed-meshheading:1971449-Dibenzazepines,
pubmed-meshheading:1971449-Dose-Response Relationship, Drug,
pubmed-meshheading:1971449-Male,
pubmed-meshheading:1971449-Mice
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pubmed:year |
1990
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pubmed:articleTitle |
Antagonism of the hypothermic effect of clozapine in mice by centrally-active alpha 2-adrenergic antagonists and alpha 1-adrenergic agonists.
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pubmed:affiliation |
Veterans Administration Medical Center, Sepulveda, CA 91343.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.
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