Linked Life Data

20018493

Source:http://linkedlifedata.com/resource/pubmed/id/20018493

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-2-3
pubmed:databankReference
pubmed:abstractText
The neurokinin-1 (NK-1) antagonist LY686017 showed activity in preclinical anxiety models. The clinical development of LY686017 included a PET study and a proof-of-concept in social anxiety disorder (SAD). [(11)C]GR205171 was used healthy volunteers receiving 1-100mg/d LY686017 for 28 days to determine brain receptor occupancy (RO). The mean NK-1 RO increased ranged from 25% with 1mg to 93% with 100mg. Subsequently, a 12-week randomized clinical trial tested LY686017 vs. paroxetine, or placebo in SAD. Pharmacokinetic (PK)/RO modeling based on the PET results predicted that once daily dosing of >30mg LY686017 led to sustained trough RO of over 80%. 189 outpatients(1) suffering from SAD were randomly assigned to 12-weeks treatment with 50mg/d LY686017 (N=77), placebo (N=74), or 20mg/d paroxetine (N=38). There was no significant difference between LY686017 and placebo as measured with the Liebowitz Social Anxiety scale (LSAS). The active comparator paroxetine showed positive trends on primary and secondary measures. The plasma concentrations were above the level expected to produce maximal brain NK-1 RO based on the PK/RO relationship obtained in the human PET investigation. Thus, further evaluation of LY686017 for the treatment of SAD does not seem warranted.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1873-7862
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
80-7
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Development of the 2nd generation neurokinin-1 receptor antagonist LY686017 for social anxiety disorder.
pubmed:affiliation
Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, IN 46285, USA. tauscherjt@lilly.com
pubmed:publicationType
Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't