Linked Life Data

17038512

Source:http://linkedlifedata.com/resource/pubmed/id/17038512

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-12-21
pubmed:abstractText
Serotonin-2C (5-HT2C) receptor antagonists and agonists have been shown to affect dopamine (DA) neurotransmission, with agonists selectively decreasing mesolimbic DA. As antipsychotic efficacy is proposed to be associated with decreased mesolimbic DA neurotransmission by virtue of DA D2 receptor antagonism, the 5-HT2C-selective receptor agonist, WAY-163909 [(7bR,10aR)-1,2, 3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7, 1hi]indole], was evaluated in animal models of schizophrenia and in vivo microdialysis and electrophysiology to determine the effects on mesolimbic and nigrostriatal DA neurotransmission. Similar to clozapine, WAY-163909 (1.7-30 mg/kg i.p.) decreased apomorphine-induced climbing with little effect on stereotypy and no significant induction of catalepsy. WAY-163909 (0.3-3 mg/kg s.c.) more potently reduced phencyclidine-induced locomotor activity compared with d-amphetamine with no effect on spontaneous activity. WAY-163909 (1.7-17 mg/kg i.p.) reversed MK-801 (5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate)- and DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]-disrupted prepulse inhibition of startle (PPI) and improved PPI in DBA/2N mice. In conditioned avoidance responding, WAY-163909 (0.3-3 mg/kg i.p.; 1-17 mg/kg p.o.) reduced avoidance responding, an effect blocked by the 5-HT(2B/2C) receptor antagonist SB 206553 [5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole]. WAY-163909 (10 mg/kg s.c.) selectively decreased extracellular levels of DA in the nucleus accumbens without affecting the striatum. Likewise, in vivo electrophysiological recordings showed a decrease in the number of spontaneously firing DA neurons in the ventral tegmental area but not in the substantia nigra with both acute and chronic (21-day) administration of WAY-163909 (1-10 mg/kg i.p.). Thus, the profile of the 5-HT2C selective receptor agonist WAY-163909 is similar to that of an atypical antipsychotic and additionally may have rapid onset properties.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
320
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
486-96
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17038512-Animals, pubmed-meshheading:17038512-Antipsychotic Agents, pubmed-meshheading:17038512-Apomorphine, pubmed-meshheading:17038512-Avoidance Learning, pubmed-meshheading:17038512-Azepines, pubmed-meshheading:17038512-Catalepsy, pubmed-meshheading:17038512-Dizocilpine Maleate, pubmed-meshheading:17038512-Indoles, pubmed-meshheading:17038512-Male, pubmed-meshheading:17038512-Mice, pubmed-meshheading:17038512-Mice, Inbred DBA, pubmed-meshheading:17038512-Microdialysis, pubmed-meshheading:17038512-Motor Activity, pubmed-meshheading:17038512-Rats, pubmed-meshheading:17038512-Rats, Sprague-Dawley, pubmed-meshheading:17038512-Serotonin 5-HT2 Receptor Agonists, pubmed-meshheading:17038512-Serotonin Receptor Agonists, pubmed-meshheading:17038512-Startle Reaction, pubmed-meshheading:17038512-Stereotyped Behavior, pubmed-meshheading:17038512-Substantia Nigra, pubmed-meshheading:17038512-Ventral Tegmental Area
pubmed:year
2007
pubmed:articleTitle
WAY-163909 [(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole]: A novel 5-hydroxytryptamine 2C receptor-selective agonist with preclinical antipsychotic-like activity.
pubmed:affiliation
Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, NJ 08543, USA. marquik@wyeth.com
pubmed:publicationType
Journal Article