Molecular mechanisms of inverse agonism via κ-opioid receptor-G protein complexes.

Opioid receptors, a subfamily of G protein-coupled receptors (GPCRs), are key therapeutic targets. In the canonical GPCR activation model, agonist binding is required for receptor-G protein complex formation, while antagonists prevent G protein coupling. However, many GPCRs exhibit basal activity, allowing G protein association without an agonist.

An opioid efficacy switch for reversible optical control of peripheral analgesia.

The mu-opioid receptor (MOR) is a major target for the treatment of pain. However, opioids are prone to side effects which limit their effectiveness as analgesics and can lead to opioid use disorders or, even, lethal overdose. The systemic administration of opioid agonists makes it both very difficult to decipher their underlying circuit mechanisms of action and to limit drug action to specific receptor subpopulations to isolate therapeutic effects from adverse side effects.

Prophylactic Effects of Ephedrine, Ondansetron and Ringer on Hemodynamic Changes during Cesarean Section under Spinal Anesthesia - a randomized clinical trial.

Background: Hemodynamic change during spinal anaesthesia for cesarean section is prevalent.

Objective: Comparing the prophylactic effects of ephedrine, ondansetron and ringer on hemodynamic changes in patients undergoing cesarean section with spinal anaesthesia.

Material And Methods: This randomized clinical trial was carried out on pregnant women undergoing elective cesarean sec-tion referred to teaching hospitals of Mashhad, Iran.

3D-QSAR studies of some reversible Acetyl cholinesterase inhibitors based on CoMFA and ligand protein interaction fingerprints using PC-LS-SVM and PLS-LS-SVM.

A great challenge in medicinal chemistry is to develop different methods for structural design based on the pattern of the previously synthesized compounds. In this study two different QSAR methods were established and compared for a series of piperidine acetylcholinesterase inhibitors. In one novel approach, PC-LS-SVM and PLS-LS-SVM was used for modeling 3D interaction descriptors, and in the other method the same nonlinear techniques were used to build QSAR equations based on field descriptors.