Research and Development, AbbVie , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
Published: April 2016
AI Article Synopsis
Article Abstract
The genetic validation for the role of the Nav1.7 voltage-gated ion channel in pain signaling pathways makes it an appealing target for the potential development of new pain drugs. The utility of nonselective Nav blockers is often limited due to adverse cardiovascular and CNS side effects. We sought more selective Nav1.7 blockers with oral activity, improved selectivity, and good druglike properties. The work described herein focused on a series of 3- and 4-substituted indazoles. SAR studies of 3-substituted indazoles yielded analog 7 which demonstrated good in vitro and in vivo activity but poor rat pharmacokinetics. Optimization of 4-substituted indazoles yielded two compounds, 27 and 48, that exhibited good in vitro and in vivo activity with improved rat pharmacokinetic profiles. Both 27 and 48 demonstrated robust activity in the acute rat monoiodoacetate-induced osteoarthritis model of pain, and subchronic dosing of 48 showed a shift to a lower EC50 over 7 days.
The study quantified total and high-intensity jump counts and assessed neuromuscular performance through countermovement jump (CMJ) force and velocity metrics by position. Twelve Division I female athletes (19.6 ± 1.
Objective: To investigate the long-term impact of cardiac surgery on the quality of life in adults with congenital heart disease (ACHDs).
Methods: Patients who had undergone cardiac surgery for congenital heart disease (CHD) at the age of 18 years or more were recruited in a single-center, cross-sectional study. The enrolled subjects completed online questionnaires to assess patient-reported outcomes: perceived health status and life satisfaction, psychological functioning, health behaviors, and illness perception.
Background: Current guidelines recommend that hyperthyroid patients should be rendered euthyroid prior to surgical procedures. These guidelines rely heavily on the use of ATDs as the primary medication, and do not give recommendations for patients who have contraindications to ATDs, or for whom standalone ATD treatment is inadequate.
Objectives: To evaluate the efficacy and safety of adjunctive pharmacological therapy and/or therapeutic plasma exchange (TPE) in the perioperative management of patients with thyrotoxicosis who were intolerant to ATD or for whom standalone ATD therapy was inadequate to achieve euthyroidism prior to surgery.
Aims: , the dominating cause of gastric cancer, most often infects children initiating inflammation in the antral part and spreads orally to the oxyntic mucosa. Traditionally, eradication of has been based upon a combination of antibiotics together with a proton pump inhibitor (PPI) to reduce gastric destruction of the antibiotics. Recently it has been shown that the more efficient inhibitors of acid secretion, the potassium-competitive acid blockers (PCABs) in combination with amoxicillin alone gave highly sufficient eradication.
The combination of the tricyclic antidepressant amitriptyline hydrochloride (AMH) and the non-selective beta-adrenergic blocker propranolol hydrochloride (PPH) is used for migraine prophylaxis. Higher doses of AMH trigger cardiac arrhythmias, anxiety, tachycardia, convulsions, hyperglycemia and anticholinergic side effects. The combined dosage formulation of AMH and PPH leads to drug-drug interactions; causes sedation, xerostomia, dysuria, insomnia and bradycardia; and results in patient non-compliance.
