Long-acting muscarinic antagonists (LAMAs) have a recognised role in the management of chronic obstructive pulmonary disease. In asthma, (both short- and long-acting) were historically considered less effective than ?2-agonists; only relatively recently studies been conducted to evaluate efficacy LAMAs, as add-on either inhaled corticosteroid (ICS) monotherapy or ICS/long-acting ?2-agonist (LAB...

Neuropathic pain affects about 7–8% of the population, and its management still poses challenges with unmet needs. Over past decades, researchers have explored cholinergic system (muscarinic nicotinic acetylcholine receptors: mAChR nAChR) compounds targeting these receptors as potential analgesics for neuropathic management. This scoping review aims to provide an overview studies on peripheral ...

Various neurodegenerative diseases and psychiatric disorders are marked by alterations in brain cholinergic function and cognitive deficits. Efforts to alleviate such deficits have been limited by a lack of selective M(1) muscarinic agonists. 5-(3-Ethyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine hydrochloride (CDD-0102A) is a partial agonist at M(1) muscarinic receptors with limited act...

The addition of either carbachol or muscarinic agonists to cultured bovine adrenal chromaffin cells results in a selective stimulation of phosphatidate (PhA) and phosphatidylinositol (PhI) labeling from 32Pi and [3H]glycerol that can be inhibited by the inclusion of atropine, but not d-tubocurarine. In contrast, increased catecholamine secretion is observed on the addition of carbachol or nicot...

We measured pharmacologically isolated GABAergic currents from layer II/III neurons of the rat auditory cortex using patch-clamp recording. Activation of muscarinic receptors by muscarine (1 microM) or oxotremorine (10 microM) decreased the amplitude of electrically evoked inhibitory postsynaptic currents to about one third of their control value. Neither miniature nor exogenously evoked GABAer...

Channels from KCNQ2 and KCNQ3 genes have been suggested to underlie the neuronal M-type K(+) current. The M current is modulated by muscarinic agonists via G-proteins and an unidentified diffusible cytoplasmic messenger. Using whole-cell clamp, we studied tsA-201 cells in which cloned KCNQ2/KCNQ3 channels were coexpressed with M(1) muscarinic receptors. Heteromeric KCNQ2/KCNQ3 currents were mod...

Fast confocal laser-scanning microscopy was used to study spatiotemporal properties of IP(3)-mediated Ca(2+) release signals in human SH-SY5Y neuroblastoma cells. [Ca(2+)](i) increases were not affected by ryanodine (30 microgM) or caffeine (10 mM) and largely insensitive to removal of external Ca(2+), indicating predominance of IP(3)-induced Ca(2+) release. Ca(2+) signals evoked by high concen...

BACKGROUND Activation of muscarinic M1 receptors is mediated via interaction of orthosteric agonists with the acetylcholine binding site or via interaction of allosteric agonists with different site(s) on the receptor. The focus of the present study was to determine if M1 receptors activated by allosteric agonists undergo the same regulatory fate as M1 receptors activated by orthosteric agonist...

Due to their potential roles in the pathophysiologies of a number of central nervous system disorders such as depression (Dilsaver, 1986), schizophrenia (Raedler et al. 2006), Alzheimer’s disease (Araujo et al. 1988) and Parkinson’s disease (Ruberg et al. 1982), modulation of the muscarinic system has been a focus of drug discovery for decades. Particular attention has been paid to developing l...