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WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride) is an achiral phenylpiperazine derivative that binds with high affinity and selectivity to the 5-HT1A receptor. WAY-100635 displaced specific binding of the 5-HT1A radioligand, [3H]8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), to rat(More)
Although considerable progress has been made in characterising the 5-HT1A receptor using agonists, partial agonists or non-selective antagonists, further studies of 5-HT1A receptor function have been hindered by the lack of highly selective antagonists. The term 'silent' antagonist has been used for such compounds in order to distinguish them unequivocally(More)
OBJECTIVE To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was(More)
(95% CI 8·8–11·4) and diastolic, 4·5 mm Hg (3·9–5·1). Active treatment reduced the total rate of stroke from 13·7 to 7·9 endpoints per 1000 patient-years (42% reduction; p=0·003). Non-fatal stroke decreased by 44% (p=0·007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p=0·03). Non-fatal(More)
BACKGROUND The extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain. METHODS We calculated hazard ratios for cause-specific death, according to baseline diabetes status or fasting glucose level, from individual-participant data on 123,205 deaths among 820,900 people in 97(More)
The novel phenylpiperazine derivative, (+/-)-WAY100135 (N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpro pionamide dihydrochloride), is a selective antagonist at both somatodendritic and postsynaptic 5-HT1A receptors. The IC50 of (+/-)-WAY100135 at the rat hippocampal 5-HT1A receptor was 34 nM, whereas its IC50 at a range of other receptor(More)
OBJECTIVE To examine the joint influences of parental monitoring and peer influence on adolescent substance use over time. SUBJECTS 6500 adolescents attending six high schools in Wisconsin and northern California. DESIGN Longitudinal study. RESULTS Parental monitoring was negatively associated with substance use, whereas the more involved an(More)
Many clinicians remain unsure of the relevance of measuring quality of life to their clinical practice. In health economics quality of life measures have become the standard means of assessing the results of health care interventions and, more controversially, the means of prioritising funding; but they have many other applications. This article--the first(More)
The distribution of 5-HT1A receptors was examined in the post-mortem human brain using whole hemisphere autoradiography and the selective 5-HT1A receptor antagonist [3H]WAY-100635 ([O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride). The autoradiograms showed very dense binding to(More)
The 5-hydroxytryptamine 5-HT1A receptor has been the focus of considerable research effort for over a decade. However, the definitive classification of this receptor and the full characterization of its pharmacology have awaited the development of highly selective 5-HT1A receptor antagonists. The only compounds available until recently have been either(More)