Biomarkers for response in major depression: comparing paroxetine and venlafaxine from two randomised placebo-controlled clinical studies.

The identification of biomarkers of response might speed drug development and set the premises to assist clinical practice in psychiatry. In this work, we evaluated a panel of peripheral biomarkers (including IL-6, IL-10, TNF-α, TNFRII, BDNF, CRP, MMP9 and PAI1) in depressed patients receiving paroxetine, venlafaxine, or placebo. Samples were obtained from two randomised placebo-controlled studies evaluating the efficacy and tolerability of a novel drug candidate, using either paroxetine or venlafaxine as active comparators.

GABA receptor occupancy by subtype selective GABA modulators: PET studies in humans.

Rationale: Sedation, dependence, and abuse liability limit the use of non-selective γ-aminobutyric acid (GABA) receptor positive modulators for the treatment of anxiety. AZD7325 and AZD6280 are novel, subtype-selective GABA receptor positive modulators with limited sedative effects.

Objectives: The current study aimed to confirm target engagement at GABA receptors by AZD7325 and AZD6280 in humans and to determine the relationship between exposure, GABA receptor occupancy, and tolerability.

Comparing the actions of lanicemine and ketamine in depression: key role of the anterior cingulate.

Intravenous infusion of lanicemine (formerly AZD6765), a low trapping non-selective N-methyl-D-aspartate (NMDA) receptor antagonist, induces antidepressant effects with a similar time course to ketamine. We investigated whether a single dose lanicemine infusion would reproduce the previously reported decrease in subgenual anterior cingulate cortex (sgACC) activity evoked by ketamine, a potential mechanism of antidepressant efficacy. Sixty un-medicated adults meeting the criteria for major depressive disorder were randomly assigned to receive constant intravenous infusions of ketamine, lanicemine or saline during a 60min pharmacological magnetic resonance imaging (phMRI) scan.

Radiochemical synthesis and in vivo evaluation of [18F]AZ11637326: an agonist probe for the α7 nicotinic acetylcholine receptor.

Introduction: The alpha-7 nicotinic acetylcholine receptor (α7 nAChR) is key in brain communication and has been implicated in the pathophysiology of diseases of the central nervous system. A positron-emitting radioligand targeting the α7 nAChR would enable better understanding of a variety of neuropsychiatric illnesses, including schizophrenia and Alzheimer's disease, and could enhance the development of new drugs for these and other conditions. We describe our attempt to synthesize an α7 nAChR-selective radiotracer for positron emission tomography (PET).

A PET study with [11C]AZ10419369 to determine brain 5-HT1B receptor occupancy of zolmitriptan in healthy male volunteers.

Aim: To investigate the occupancy at brain 5-hydroxytryptamine (5-HT) 1B receptors in human subjects after administration of the antimigraine drug zolmitriptan.

Methods: Positron emission tomography (PET) studies were undertaken using the radioligand [(11)C]AZ10419369 in eight control subjects at baseline and after administration of zolmitriptan orodispersible tablets. The subjects were examined after two consecutive administrations of 10 mg zolmitriptan, approximately 1 week apart.

Glutamate-based depression GBD.

We describe a new term: glutamate-based depression (GBD). GBD is defined as a chronic depressive illness associated with environmental stress and diseases associated with altered glutamate neurotransmission. We hypothesize that glutamate-induced over-activation of extrasynaptic NMDA receptors in the subgenual cingulate area called Brodmann's 25 plays an important role in the etiology of depression and may be responsible for the high incidence of co-morbid depression associated in diseases with glutamate etiology.

2,6-Disubstituted pyrazines and related analogs as NR2B site antagonists of the NMDA receptor with anti-depressant activity.

Herein we describe the discovery of compounds that are competitive antagonists of the CP101-606 binding site within the NR2B subtype of the NMDA receptor. The compounds identified do not possess phenolic functional groups such as those in ifenprodil and related analogs. Initial identification of hits in this series focused on a basic, secondary amine side chain which led to good potency, but also presented a hERG liability.

[11C]AZ10419369: a selective 5-HT1B receptor radioligand suitable for positron emission tomography (PET). Characterization in the primate brain.

The 5-HT1B receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. Here we report the synthesis of a novel PET radioligand, [11C]AZ10419369 (5-methyl-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide), for in vivo visualization of 5-HT1B receptors in the brains of macaques and humans subjects. [11C]AZ10419369 was prepared by N-methylation of (8-(1-piperazinyl)-5-methylchrom-2-en-4-one-2-(4-morpholinophenyl) carboxamide, using carbon-11 methyl triflate.

Synthesis and biodistribution of radiolabeled alpha 7 nicotinic acetylcholine receptor ligands.

Unlabelled: Our objective was to develop an array of alpha(7)-selective nicotinic cholinergic receptor (nAChR)-based imaging agents for PET and SPECT.

Methods: (2'R)-N-(11)C-Methyl-N-(phenylmethyl)-spiro[1-azabicyclo[2.2.