Nicotinic alpha 7 receptor agonists EVP-6124 and BMS-933043, attenuate scopolamine-induced deficits in visuo-spatial paired associates learning - Fig 1

<p>Chemical structures of A) BMS-933043, B) RG3847, C) EVP-6124 and D) donepezil.</p

Effect of treatment with RG3487 on scopolamine-induced impairment of learning in the vsPAL task (N = 8).

<p>Results are presented as the mean ± SEM % eventual correct responses achieved within 6 attempts after presentation of trials with 2-, 3- or 4- stimuli. Results were analyzed by 2 way RM ANOVA followed by Holm-Sidak’s post-hoc analysis; † <i>p<0</i>.<i>05</i> and †† <i>p<0</i>.<i>01</i> compared to vehicle/vehicle treatment.</p

Comparison of the dose-effect curves to reverse scopolamine-induced impairment of learning in the vsPAL task (% correct eventual).

<p>For each subject, treatment effects on the % correct eventual response were expressed as a difference from the vehicle+scopolamine condition, and group means and SEMs were replotted for side-by-side comparisons. Y axis is percent change from vehicle+scopolamine condition. X axis indicates test condition. Hatched bars indicate a test combination differed significantly from vehicle+scopolamine in post-hoc tests from RM ANOVA dose-response functions (e.g. at <i>p</i><0.05 or <i>p</i><0.01).</p

Discovery of (5<i>S</i>,6<i>S</i>,9<i>R</i>)‑5-Amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro‑5<i>H</i>‑cyclohepta[<i>b</i>]pyridin-9-yl 4‑(2-oxo-2,3-dihydro‑1<i>H</i>‑imidazo[4,5‑<i>b</i>]pyridin-1-yl)piperidine-1-carboxylate (BMS-927711): An Oral Calcitonin Gene-Related Peptide (CGRP) Antagonist in Clinical Trials for Treating Migraine

Calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated clinical efficacy in the treatment of acute migraine. Herein, we describe the design, synthesis, and preclinical characterization of a highly potent, oral CGRP receptor antagonist BMS-927711 (<b>8</b>). Compound <b>8</b> has good oral bioavailability in rat and cynomolgus monkey, attractive overall preclinical properties, and shows dose-dependent activity in a primate model of CGRP-induced facial blood flow. Compound <b>8</b> is presently in phase II clinical trials