Search results for "Modulator"
showing 10 items of 210 documents
Fingolimod as a Treatment in Neurologic Disorders Beyond Multiple Sclerosis
2020
Abstract Fingolimod is an approved treatment for relapsing–remitting multiple sclerosis (MS), and its properties in different pathways have raised interest in therapy research for other neurodegenerative diseases. Fingolimod is an agonist of sphingosine-1-phosphate (S1P) receptors. Its main pharmacologic effect is immunomodulation by lymphocyte homing, thereby reducing the numbers of T and B cells in circulation. Because of the ubiquitous expression of S1P receptors, other effects have also been described. Here, we review preclinical experiments evaluating the effects of treatment with fingolimod in neurodegenerative diseases other than MS, such as Alzheimer’s disease or epilepsy. Fingolimo…
El modulador alostérico negativo de los mGluR5, MPEP, potencia la reinstauración de la preferencia condicionada inducida con priming de cocaína
2019
Cocaine addiction is a chronic disorder with high relapse rates; therefore, understanding the neuronal mechanisms underlying drug-seeking during relapse is a priority to develop targeted pharmacotherapy. The metabotropic glutamate receptor 5 (mGluR5) seems to be involved in the reinstatement induced by cocaine-associated cues. The main objective of the study was to evaluate the efficacy of MPEP, a negative allosteric modulator of mGluR5, in attenuating or potentiating the reinstatement induced by priming doses of cocaine in the CPP paradigm, ultimately to further knowledge regarding the role of the mGluR5 in relapse into cocaine abuse. OF1 mice (48 female and 48 male) were conditioned in th…
Molecular bases of anorexia nervosa, bulimia nervosa and binge eating disorder: shedding light on the darkness
2017
International audience; Eating-disorders (EDs) consequences to human health are devastating, involving social, mental, emotional, physical and life-threatening aspects, concluding on impairment and death in cases of extreme anorexia nervosa. It also implies that people suffering an ED need to find psychiatric and psychological help as soon as possible to achieve a fully physical and emotional recovery. Unfortunately, to date, there is a crucial lack of efficient clinical treatment to these disorders. In this review, we present an overview concerning the actual pharmacological and psychological treatments, the knowledge of cells, circuits, neuropeptides, neuromodulators and hormones in the h…
Eight-Membered Rings With Two Heteroatoms 1,3
2022
Eight-membered rings with two heteroatoms in a 1,3-relationship, namely 1,3-diazocine, 2H-1,3-oxazocine, 2H-1,3-thiazocine, 4H-1,3-dioxocin, 4H-1,3-oxathiocin, and 4H-1,3-dithiocin, are discussed in this chapter, that covers the literature from 2007 to October 2020 (SciFindern search) and reports the chemistry of uncondensed derivatives, heterocines fused to carbocycles and heterocycles, as well as bridged heterocines. Among eight-membered 1,3-diheterocines, 1,3-diazocines and 1,3-oxazocines are the two largest classes, based on the number of publications, mostly due to the studies of the synthesis of these cyclic systems, their pharmacological properties and/or their important industrial a…
Identification of multiplicatively acting modulatory mutational signatures in cancer
2022
Abstract Background A deep understanding of carcinogenesis at the DNA level underpins many advances in cancer prevention and treatment. Mutational signatures provide a breakthrough conceptualisation, as well as an analysis framework, that can be used to build such understanding. They capture somatic mutation patterns and at best identify their causes. Most studies in this context have focused on an inherently additive analysis, e.g. by non-negative matrix factorization, where the mutations within a cancer sample are explained by a linear combination of independent mutational signatures. However, other recent studies show that the mutational signatures exhibit non-additive interactions. Resu…
Cannabinoid CB1 receptor activation modulates spontaneous contractile activity in mouse ileal longitudinal muscle.
2007
The purpose of the present study was to examine whether cannabinoid receptor agonists influence spontaneous contractile activity of longitudinal muscle in mouse ileum in vitro. Isolated segments of mouse ileum displayed spontaneous contractions with an amplitude and frequency of about 300 mg and 30 cpm, respectively. The endocannabinoid anandamide (1-100 microM), the selective cannabinoid CB(1) receptor agonist, ACEA (0.1 microM-10 microM), but not the selective cannabinoid CB(2) receptor agonist, JWH 133 (0.1 microM-10 microM), reduced in a concentration-dependent manner the spontaneous mechanical activity. The inhibitory effect consisted in a decrease of the mean amplitude of longitudinal…
The selective estrogen receptor modulator, bazedoxifene, reduces ischemic brain damage in male rat
2014
While the estrogen treatment of stroke is under debate, selective estrogen receptor modulators (SERMs) arise as a promising alternative. We hypothesize that bazedoxifene (acetate, BZA), a third generation SERM approved for the treatment of postmenopausal osteoporosis, reduces ischemic brain damage in a rat model of transient focal cerebral ischemia. For comparative purposes, the neuroprotective effect of 17β-estradiol (E2) has also been assessed. Male Wistar rats underwent 60min middle cerebral artery occlusion (intraluminal thread technique), and grouped according to treatment: vehicle-, E2- and BZA-treated rats. Optimal plasma concentrations of E2 (45.6±7.8pg/ml) and BZA (20.7±2.1ng/ml) w…
Cyclic AMP-mediated upregulation of the expression of neuronal NO synthase in human A673 neuroepithelioma cells results in a decrease in the level of…
2004
The expression level of neuronal nitric oxide synthase (nNOS) can vary depending on the (patho)physiological conditions. Here we document a marked induction of nNOS mRNA, protein, and total NO production in response to dibutyryl cyclic AMP (db-cAMP) in human A673 neuroepithelial cells. However, the upregulation of nNOS was associated with a decreased level of production of bioactive NO and by an increase in the level of generation of reactive oxygen species (ROS). ROS production could be prevented by the NOS inhibitor L-NAME, suggesting nNOS itself is involved in ROS generation. Sepiapterin supplementation of db-cAMP-treated A673 cells could restore full bioactive NO production, most likely…
Evidence for a modulatory role of cannabinoids on the excitatory NANC neurotransmission in mouse colon
2007
Abstract It is well accepted that endogenous cannabinoids and CB1 receptors are involved in the regulation of smooth muscle contractility and intestinal motility, through a mechanism mainly related to reduction of acetylcholine release from cholinergic nerve endings. Because, few data exist on a possible modulatory action of the cannabinoid agents on the non-adrenergic non-cholinergic (NANC) excitatory and inhibitory neurotransmission, the aim of the present study was to investigate the effects of cannabinoid drugs on the NANC responses elicited by electrical field stimulation (EFS) in the circular muscle of mouse proximal colon. Colonic contractions were monitored as changes in endoluminal…
The Endocannabinoid System Promotes Astroglial Differentiation by Acting on Neural Progenitor Cells
2006
Endocannabinoids exert an important neuromodulatory role via presynaptic cannabinoid CB1receptors and may also participate in the control of neural cell death and survival. The function of the endocannabinoid system has been extensively studied in differentiated neurons, but its potential role in neural progenitor cells remains to be elucidated. Here we show that the CB1receptor and the endocannabinoid-inactivating enzyme fatty acid amide hydrolase are expressed, bothin vitroandin vivo, in postnatal radial glia (RC2+cells) and in adult nestin type I (nestin+GFAP+) neural progenitor cells. Cell culture experiments show that CB1receptor activation increases progenitor proliferation and differ…