Linked Life Data

8531087

Source:http://linkedlifedata.com/resource/pubmed/id/8531087

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-2-1
pubmed:abstractText
Nafadotride (N[(n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyano naphtalene-2-carboxamide) is a novel compound, which inhibits potently and stereoselectively [125I]iodosulpride binding at recombinant human dopamine D3 receptors. the levoisomer displays an apparent Ki value of 0.3 nM at the dopamine D3 receptor, but is 10 times less potent at the human recombinant dopamine D2 receptor. In comparison, the dextroisomer displays 20-fold less apparent affinity at the dopamine D3 receptor and reduced (2-fold) selectivity. l-Nafadotride displays iow, micromolar affinity at dopamine D1 and D4 receptors and negligible apparent affinity at various other receptors. In dopamine D3 receptor-transfected NG-108 15 cells, in which dopamine agonists increase mitogenesis, l-nafadotride has no intrinsic activity, but competitively antagonizes the quinpirole-induced mitogenetic response, monitored by [3H]thymidine incorporation with a pA2 of 9.6. In dopamine D2 receptor-transfected Chinese Hamster Ovary cells, l-nafadotride also behaves as a competitive antagonist of quinpirole-induced mitogenesis with an 11-fold lower potency. These studies establish nafadotride as a pure, extremely potent, competitive and preferential dopamine D3 receptor antagonist in vitro. l-Nafadotride displaces in vivo N-[3H]propylnorapomorphine accumulation at lower dosage and for longer periods in limbic structures, containing both dopamine D2 and D3 receptors than in the stratum, containing dopamine D2 receptor only. At low dosage (0.1-1 mg/kg), nafadotride, unlike haloperidol, a dopamine D2 receptor-preferring antagonist, increases spontaneous locomotion of habituated rats and climbing behavior of mice, at doses that do not modify striatal homovanillic acid levels. At high dosage (1-100 mg/kg), nafadotride, like haloperidol, produces catalepsy and antagonizes apomorphine-induced climbing.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
1239-46
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8531087-Animals, pubmed-meshheading:8531087-Apomorphine, pubmed-meshheading:8531087-CHO Cells, pubmed-meshheading:8531087-Cell Line, pubmed-meshheading:8531087-Corpus Striatum, pubmed-meshheading:8531087-Cricetinae, pubmed-meshheading:8531087-Dopamine Agonists, pubmed-meshheading:8531087-Dopamine Antagonists, pubmed-meshheading:8531087-Humans, pubmed-meshheading:8531087-Limbic System, pubmed-meshheading:8531087-Male, pubmed-meshheading:8531087-Mice, pubmed-meshheading:8531087-Mitosis, pubmed-meshheading:8531087-Motor Activity, pubmed-meshheading:8531087-Naphthalenes, pubmed-meshheading:8531087-Pyrrolidines, pubmed-meshheading:8531087-Rats, pubmed-meshheading:8531087-Receptors, Dopamine D2, pubmed-meshheading:8531087-Receptors, Dopamine D3, pubmed-meshheading:8531087-Tumor Cells, Cultured
pubmed:year
1995
pubmed:articleTitle
Nafadotride, a potent preferential dopamine D3 receptor antagonist, activates locomotion in rodents.
pubmed:affiliation
Unité de Neurobiogie et Pharmacologie, Centre Paul Broca de l'Institut National de la Santé et de la Recherche Médicale, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't