Distinct mechanism for antidepressant activity by blockade of central substance P receptors

…, L Hewson, D Smith, EJ Carlson, RJ Hargreaves… - Science, 1998 - science.org
The localization of substance P in brain regions that coordinate stress responses and receive
convergent monoaminergic innervation suggested that substance P antagonists might …

Clinical biomarkers in drug discovery and development

R Frank, R Hargreaves - Nature reviews Drug discovery, 2003 - nature.com
Biomarkers enable the characterization of patient populations and quantitation of the extent
to which new drugs reach intended targets, alter proposed pathophysiological mechanisms …

Thalamic sensitization transforms localized pain into widespread allodynia

…, V Kainz, Z Bajwa, R Hargreaves… - Annals of …, 2010 - Wiley Online Library
Objective Focal somatic pain can evolve into widespread hypersensitivity to nonpainful and
painful skin stimuli (allodynia and hyperalgesia, respectively). We hypothesized that …

[18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor

…, TM Fong, RJ Hargreaves - Proceedings of the …, 2007 - National Acad Sciences
[ 18 F]MK-9470 is a selective, high-affinity, inverse agonist (human IC 50 , 0.7 nM) for the
cannabinoid CB1 receptor (CB1R) that has been developed for use in human brain imaging. …

Neurogenic inflammation in the context of migraine

DJ Williamson, RJ Hargreaves - Microscopy research and …, 2001 - Wiley Online Library
Despite considerable research into the pathogenesis of idiopathic headaches, such as
migraine, the pathophysiological mechanisms underlying them remain poorly understood. …

Lack of efficacy of the substance p (neurokinin1 receptor) antagonist aprepitant in the treatment of major depressive disorder

…, W Ball, M Morrison, D Snavely, G Liu, R Hargreaves… - Biological …, 2006 - Elsevier
BACKGROUND: An early clinical trial suggested that the substance P (neurokinin 1 receptor)
antagonist, aprepitant, might provide a unique mechanism of antidepressant activity. …

[HTML][HTML] Interictal dysfunction of a brainstem descending modulatory center in migraine patients

EA Moulton, R Burstein, S Tully, R Hargreaves… - PloS one, 2008 - journals.plos.org
Background The brainstem contains descending circuitry that can modulate nociceptive
processing (neural signals associated with pain) in the dorsal horn of the spinal cord and the …

A role for fMRI in optimizing CNS drug development

D Borsook, L Becerra, R Hargreaves - Nature reviews Drug discovery, 2006 - nature.com
Drug development today needs to balance agility, speed and risk in defining the probability
of success for molecules, mechanisms and therapeutic concepts. New techniques in …

Structural Optimization Affording 2-(R)-(1-(R)-3,5-Bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a Potent …

…, AR Williams, W Rycroft, R Hargreaves… - Journal of medicinal …, 1998 - ACS Publications
Structural modifications requiring novel synthetic chemistry were made to the morpholine
acetal human neurokinin-1 (hNK-1) receptor antagonist 4, and this resulted in the discovery of 2…

[PDF][PDF] The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake

…, J Blundell, GA Herman, HD Burns, RJ Hargreaves… - Cell Metabolism, 2008 - cell.com
Cannabinoid 1 receptor (CB1R) inverse agonists are emerging as a potential obesity therapy.
However, the physiological mechanisms by which these agents modulate human energy …