Linked Life Data

19939862

Source:http://linkedlifedata.com/resource/pubmed/id/19939862

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-7-28
pubmed:abstractText
Nomifensine potently inhibits the reuptake of norepinephrine and dopamine in vitro. It is one of few antidepressants with marked potency to block dopamine reuptake that has ever been used clinically. Acute and sustained administration of nomifensine was investigated on the firing of monoaminergic neurons to understand its mechanism of action. In vivo extracellular recordings of locus coeruleus, ventral tegmental area and dorsal raphe nucleus neurons were obtained from male Sprague-Dawley rats. The intravenous injection of nomifensine in the locus coeruleus and ventral tegmental area yielded ED(50) values of 40 +/- 1 and 450 +/- 41 microg/kg, respectively, suggesting that nomifensine directly acted upon dopamine and norepinephrine neurons, since these values are proportional to its affinities for norepinephrine and dopamine transporters. There was no effect on 5-HT neurons. Nomifensine (5 mg/kg/day, subcutaneous, using minipumps) potently and significantly inhibited dopamine neuronal firing in the ventral tegmental area after 2 days, with recovery to normal after the 14-day treatment due to D(2) autoreceptor desensitization. Norepinephrine neuronal firing in the locus coeruleus was significantly decreased after 2 and 14 days. A significant increase in dorsal raphe nucleus 5-HT neuronal firing was seen after a two-day regimen, and remained elevated after 14 days. Desensitization of the 5-HT(1A) receptor on 5-HT neurons of the dorsal raphe nucleus occurred after two days of nomifensine administration. Nomifensine likely treated depression by acting on dopamine, norepinephrine and 5-HT neurons, highlighting the importance of the functional connectivity between these three monoaminergic systems.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1461-7285
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1223-35
pubmed:meshHeading
pubmed-meshheading:19939862-Action Potentials, pubmed-meshheading:19939862-Adrenergic Uptake Inhibitors, pubmed-meshheading:19939862-Animals, pubmed-meshheading:19939862-Delayed-Action Preparations, pubmed-meshheading:19939862-Dopamine, pubmed-meshheading:19939862-Dose-Response Relationship, Drug, pubmed-meshheading:19939862-Drug Evaluation, Preclinical, pubmed-meshheading:19939862-Electrophysiological Phenomena, pubmed-meshheading:19939862-Locus Coeruleus, pubmed-meshheading:19939862-Male, pubmed-meshheading:19939862-Morpholines, pubmed-meshheading:19939862-Neurons, pubmed-meshheading:19939862-Neurotransmitter Uptake Inhibitors, pubmed-meshheading:19939862-Nomifensine, pubmed-meshheading:19939862-Norepinephrine, pubmed-meshheading:19939862-Raphe Nuclei, pubmed-meshheading:19939862-Rats, pubmed-meshheading:19939862-Rats, Sprague-Dawley, pubmed-meshheading:19939862-Receptor, Serotonin, 5-HT1A, pubmed-meshheading:19939862-Receptors, Dopamine D2, pubmed-meshheading:19939862-Serotonin, pubmed-meshheading:19939862-Time Factors, pubmed-meshheading:19939862-Ventral Tegmental Area
pubmed:year
2010
pubmed:articleTitle
Effects of acute and sustained administration of the catecholamine reuptake inhibitor nomifensine on the firing activity of monoaminergic neurons.
pubmed:affiliation
University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't