The binding problem is the brain's fundamental challenge to integrate sensory information to form a unified representation of a stimulus. A recent nonhuman animal model suggests that acetylcholine serves as the neuromodulatory substrate for feature binding. We hypothesized that this animal model of cholinergic contributions to feature binding may be an analogue of human attention. To test this ...

OBJECTIVES This article aims to analyse the use of solifenacin in the treatment of overactive bladder in order to show its efficacy and safety within the framework of the scientific evidence. METHODS The available scientific literature was reviewed, including most of the relevant clinical trials performed with solifenacin. RESULTS All the studies analysed show significant improvements in pa...

INTRODUCTION Overactive bladder (OAB) is a prevalent and persistent condition that is often under-diagnosed and under-treated, and which frequently requires tailored treatment for successful management. METHODS This consensus opinion-based review summarizes the discussions of a group of experts in the field of OAB that were assembled to evaluate the importance of correct diagnosis and appropr...

We investigated the binding properties of the (R)- and (S)-enantiomers of the muscarinic antagonists trihexyphenidyl, procyclidine, hexahydro-difenidol, p-fluoro-hexahydro-difenidol, hexbutinol, p-fluoro-hexbutinol, and their corresponding methiodides at muscarinic M1, M2, M3 and M4 receptor subtypes. In addition, binding properties of the (R)- and (S)-enantiomers of oxyphencyclimine were studi...

The role of aging on contraction or relaxation through muscarinic or alpha-adrenergic receptors, respectively, was studied in isolated rat jejunum. Furthermore, the influence of extracellular calcium was analyzed, through functional and radioligand binding assays. The rank order of potency for selective muscarinic antagonists for M(1), M(2), and M(3) receptor subtypes, measured from affinity (p...

BACKGROUND Pharmaceuticals with targets in the cholinergic transmission have been used for decades and are still fundamental treatments in many diseases and conditions today. Both the transmission and the effects of the somatomotoric and the parasympathetic nervous systems may be targeted by such treatments. Irrespective of the knowledge that the effects of neuronal signalling in the nervous sy...

Specificities of cholinergic receptors for the accumulation of inositol trisphosphates (InsP3) and cyclic GMP and mobilization of intracellular Ca2+ in relation to culture periods were investigated in primary cultures of bovine adrenal chromaffin cells. At 0.5 day in culture, muscarine, a specific agonist for muscarinic receptors, caused a greater effect on intracellular Ca2+ mobilization and t...

We have examined the effects of raising G protein concentration on the pharmacology of a series of agonist and antagonist ligands at the m1, m3, and m5 muscarinic subtypes using a functional assay. Overexpression of G(alpha q) induced constitutive activity of these receptors. The constitutive activity was reversed completely by every muscarinic antagonist tested, which indicates that they are a...

We investigated the subtypes of the muscarinic receptor mediating short-term heterologous desensitization in the isolated ileum. Treatment of the ileum from C57BL/6 mice with acetylcholine (30 microM) for 20 min caused a subsequent decrease in contractile sensitivity to both prostaglandin F2alpha (PGF2alpha) and the muscarinic agonist, oxotremorine-M. This subsensitivity was characterized by 7-...

BACKGROUND An imbalance of sympathetic and parasympathetic drive to the heart is an important risk factor for cardiac death in patients with coronary heart disease, diabetes, and renal insufficiency. The amount of neurotransmitter released from peripheral autonomic nerves is modulated by presynaptic receptor systems. In analogy to alpha-autoreceptors on sympathetic nerves, muscarinic autorecept...