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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1989-12-1
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pubmed:abstractText |
The enantiomers of the potent and selective dopamine (DA) D-2 receptor agonist 2-(N-propyl-N-2-thienylethyl-amino)-5-hydroxytetralin, N-0437, were tested for their pharmacological actions on DA D-2 autoreceptors in vivo, by measuring DA release by microdialysis during local administration of both drugs and in vitro, by measuring their effects on the electrically stimulated release of [3H]DA from striatal slices. In both experimental situations (-)-N-0437, at low doses, acted as an agonist on receptors controlling DA release. However, in vivo at a concentration of 10 microM (-)-N-0437 induced a short-lasting increase in DA release and in vitro the inhibitory effect of (-)-N-0437 was significantly less pronounced at higher concentrations (1-10 microM). (+)-N-0437 (0.1-10 microM) showed an antagonistic action both in vivo and in vitro. Following inhibition of the neuronal impulse flow with tetrodotoxin, (+)-N-0437 failed to increase DA release suggesting the effect of this enantiomer is not associated with an amphetamine-like action on the nerve terminal. The use of the DA re-uptake inhibitor GBR 12909 confirmed the antagonism of (+)-N-0437 towards DA receptors. Since it is known that (+)-N-0437 acts as an agonist on DA D-2 autoreceptors controlling the synthesis of DA, these results provide additional evidence for the existence of distinct DA D-2 autoreceptor populations involved in the release and synthesis of DA. The differential actions of (-)- and (+)-N-0437 gave rise to mutual antagonism of the actions of the enantiomers both in vivo and in vitro, thus providing a strong argument for using the enantiomers instead of the racemate in clinical situations.
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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/Apomorphine,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Kainic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/N 0437,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotransmitter Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrahydronaphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrodotoxin,
http://linkedlifedata.com/resource/pubmed/chemical/Thiophenes,
http://linkedlifedata.com/resource/pubmed/chemical/vanoxerine
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0014-2999
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
166
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-11
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2572424-Animals,
pubmed-meshheading:2572424-Apomorphine,
pubmed-meshheading:2572424-Catheterization,
pubmed-meshheading:2572424-Corpus Striatum,
pubmed-meshheading:2572424-Dialysis,
pubmed-meshheading:2572424-Dopamine,
pubmed-meshheading:2572424-Dopamine Agents,
pubmed-meshheading:2572424-Electric Stimulation,
pubmed-meshheading:2572424-Kainic Acid,
pubmed-meshheading:2572424-Male,
pubmed-meshheading:2572424-Naphthalenes,
pubmed-meshheading:2572424-Neurotransmitter Uptake Inhibitors,
pubmed-meshheading:2572424-Piperazines,
pubmed-meshheading:2572424-Rabbits,
pubmed-meshheading:2572424-Rats,
pubmed-meshheading:2572424-Rats, Inbred Strains,
pubmed-meshheading:2572424-Stereoisomerism,
pubmed-meshheading:2572424-Tetrahydronaphthalenes,
pubmed-meshheading:2572424-Tetrodotoxin,
pubmed-meshheading:2572424-Thiophenes,
pubmed-meshheading:2572424-Time Factors
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pubmed:year |
1989
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pubmed:articleTitle |
The enantiomers of the dopamine agonist N-0437: in vivo and in vitro effects on the release of striatal dopamine.
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pubmed:affiliation |
Department of Pharmacy, State University of Groningen, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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