Illustration of the study design.

<p>Illustration of the study design.</p

Descriptive statistics for the diffusion model parameters.

<p>Descriptive statistics for the diffusion model parameters.</p

Upper graph: Recognition errors (group mean +/- SE following stimulation of Oz (control site) and pSTG (experimental site).

<p>Lower graph: Each participant's recognition errors following stimulation of Oz and pSTG. The line marked by diamond end-points represents the performance of three participants with the same scores.</p

The mean location of the target and orientation of the stimulator during rTMS of: (A) caudalmost portion of the temporal gyrus, pSTG; (B) control site, Oz; and (C) inferior frontal gyrus, IFG.

<p>The mean location of the target and orientation of the stimulator during rTMS of: (A) caudalmost portion of the temporal gyrus, pSTG; (B) control site, Oz; and (C) inferior frontal gyrus, IFG.</p

Descriptive statistics for the different error types.

<p>Descriptive statistics for the different error types.</p

Descriptive statistics for the basic performance measures.

<p>Descriptive statistics for the basic performance measures.</p

Normalized false alarm and omission errors (group mean +/- SE) for IFG and pSTG stimulation.

<p>Normalized false alarm and omission errors (group mean +/- SE) for IFG and pSTG stimulation.</p

Legislative Documents

Also, variously referred to as: House bills; House documents; House legislative documents; legislative documents; General Court documents

Synthesis and Pharmacological Characterization of Two Novel, Brain Penetrating P2X₇ Antagonists

The synthesis and preclinical characterization of two novel, brain penetrating P2X₇ compounds will be described. Both compounds are shown to be high potency P2X₇ antagonists in human, rat, and mouse cell lines and both were shown to have high brain concentrations and robust receptor occupancy in rat. Compound <b>7</b> is of particular interest as a probe compound for the preclinical assessment of P2X₇ blockade in animal models of neuro-inflammation

A Dipolar Cycloaddition Reaction To Access 6‑Methyl-4,5,6,7-tetrahydro‑1<i>H</i>‑[1,2,3]­triazolo[4,5‑<i>c</i>]­pyridines Enables the Discovery Synthesis and Preclinical Profiling of a P2X7 Antagonist Clinical Candidate

A single pot dipolar cycloaddition reaction/Cope elimination sequence was developed to access novel 1,4,6,7-tetrahydro-5<i>H</i>-[1,2,3]­triazolo­[4,5-<i>c</i>]­pyridine P2X7 antagonists that contain a synthetically challenging chiral center. The structure–activity relationships of the new compounds are described. Two of these compounds, (<i>S</i>)-(2-fluoro-3-(trifluoromethyl)­phenyl)­(1-(5-fluoropyrimidin-2-yl)-6-methyl-1,4,6,7-tetrahydro-5<i>H</i>-[1,2,3]­triazolo­[4,5-<i>c</i>]­pyridin-5-yl)­methanone (compound <b>29</b>) and (<i>S</i>)-(3-fluoro-2-(trifluoromethyl)­pyridin-4-yl)­(1-(5-fluoropyrimidin-2-yl)-6-methyl-1,4,6,7-tetrahydro-5<i>H</i>-[1,2,3]­triazolo­[4,5-<i>c</i>]­pyridin-5-yl)­methanone (compound <b>35</b>), were found to have robust P2X7 receptor occupancy at low doses in rat with ED₅₀ values of 0.06 and 0.07 mg/kg, respectively. Compound <b>35</b> had notable solubility compared to <b>29</b> and showed good tolerability in preclinical species. Compound <b>35</b> was chosen as a clinical candidate for advancement into phase I clinical trials to assess safety and tolerability in healthy human subjects prior to the initiation of proof of concept studies for the treatment of mood disorders