Search results for "Piperidine"
showing 10 items of 236 documents
Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma : an international, randomised, open-label, phase 3 study
2016
Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma.This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index…
Combination of intensive cognitive rehabilitation and donepezil therapy in Alzheimer's disease (AD).
2009
Acetylcholinesterase inhibitors (AchEIs) are extensively used in Alzheimer's disease (AD) while reality orientation therapy (ROT) is a cognitive rehabilitation indicated for mentally deteriorated patients. We aimed to evaluate the efficacy of the combination of donepezil with an intensive ROT with active participation of the caregiver. Patients with AD (n=100, mean age 78.4±4.3 years) initiated treatment with donepezil, 5mg/day; 62 of them underwent a 3-week, daily ROT and physical reactivation training with the caregiver (Group A); 38 participants received only donepezil therapy (Group B). All subjects were tested for cognitive and functional abilities at baseline, at the end of the traini…
Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice
2010
AbstractBackgroundNumerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice.MethodsIn the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, r…
Benzimidazolones and renzapride facilitate acetylcholine release from guinea-pig myenteric plexus via 5-HT4 receptors
1995
The effects of the 5-HT4 receptor agonists BIMU 8, BIMU 1, renzapride and of the 5-HT1p receptor agonist 5-hydroxyindalpine on basal and electrically evoked outflow of tritium were studied in guinea-pig longitudinal muscle myenteric plexus preparations preincubated with [3H]choline. Muscle contractions were recorded simultaneously. BIMU 8 caused a calcium dependent and tetrodotoxin sensitive increase in basal [3H]outflow that was assumed to represent release of [3H]acetylcholine. In addition, BIMU 8 enhanced the release of [3H]acetylcholine and twitch contractions evoked by submaximal electrical stimulation. Ondansetron (1 μmol/l) did not change the effects of BIMU 8, but DAU 6285 and tropi…
Altered tachykinergic influence on gastric mechanical activity in mdx mice
2006
Abstract This study investigated whether alterationsin gastric activity in dystrophic mdx mouse can beattributed to dysfunctions of tachykinins. Endolumi-nal pressure was recorded and the expression ofneuronal nitric oxide synthase (nNOS), NK1 and NK2neurokinin receptors was investigated by immunoh-istochemistry. SR48968, NK2 receptor antagonist, butnot SR140333, NK1 receptor antagonist, decreased thetone only in mdx gastric preparations. In the presenceof N x -nitro- L -arginine methyl ester ( L -NAME), inhib-itor of NOS, SR48968 reduced the tone also in normalstomach. [Sar 9 , Met(O 2 ) 11 ]-SP, agonist of NK1 recep-tors, caused tetrodotoxin-sensitive relaxations, antag-onized by SR140333…
Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (r)-(+)-[2,3-dihydro-5-methyl-3-(4-m…
2003
The aim of the present in vivo microdialysis study was to investigate whether prenatal exposure to the CB1 receptor agonist WIN55,212-2 mesylate (WIN; (R)-()-(2,3- dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo(1,2,3-de)- 1,4-benzoxazin-6-yl)-1-naphthalenylmethanone), at a dose of 0.5 mg/kg (s.c. from the fifth to the 20th day of gestation), that causes neither malformations nor overt signs of toxicity, influences cortical glutamate extracellular levels in adult (90- day old) rats. Dam weight gain, pregnancy length and litter size at birth were not significantly affected by prenatal treatment with WIN. Basal and K-evoked dialysate glutamate levels were lower in the cerebral cortex of adul…
Endogenous noradrenaline release from guinea-pig isolated trachea is inhibited by activation of M2 receptors
1992
Overflow of endogenous noradrenaline (NA) from guinea-pig isolated tracheae was evoked by electrical field stimulation (3 Hz, 540 pulses). The muscarinic receptor agonist oxotremorine inhibited the evoked overflow of NA in a concentration-dependent manner (EC50 84 nM). Methoctramine, pirenzepine and p-fluoro-hexahydrosiladiphenidol (each 1 microM) shifted the concentration-response curves of oxotremorine to the right with apparent pA2 values of 7.60, 6.74 and 6.18, respectively. It is concluded that sympathetic nerve terminals in the guinea-pig trachea are endowed with inhibitory muscarinic M2 receptors.
Therapeutic Potential of Inhibitors of Endocannabinoid Degradation for the Treatment of Stress-Related Hyperalgesia in an Animal Model of Chronic Pain
2014
The occurrence of chronic stress, depression, and anxiety can increase nociception in humans and may facilitate the transition from localized to chronic widespread pain. The mechanisms underlying chronic widespread pain are still unknown, hindering the development of effective pharmacological therapies. Here, we exposed C57BL/6J mice to chronic unpredictable stress (CUS) to investigate how persistent stress affects nociception. Next, mice were treated with multiple intramuscular nerve growth factor (NGF) injections, which induced chronic widespread nociception. Thus, combination of CUS and NGF served as a model where psychophysiological impairment coexists with long-lasting hyperalgesia. We…
Involvement of CB1 and CB2 receptors in the modulation of cholinergic neurotransmission in mouse gastric preparations.
2007
Abstract While most of the studies concerning the role of cannabinoids on gastric motility have focused the attention on the gastric emptying in in vivo animal models, there is little information about the cannabinoid peripheral influence in the stomach. In addition, the functional features of CB2 receptors in the gastrointestinal tract have been poorly characterized. The purpose of the present study was to investigate the effects of cannabinoid drugs on the excitatory cholinergic and inhibitory non-adrenergic non-cholinergic (NANC) neurotransmission in mouse isolated gastric preparations. Intraluminal pressure from isolated whole stomach was recorded and mechanical responses induced by ele…
Preliminary in vivo and ex vivo evaluation of the 5-HT2A imaging probe [18F]MH.MZ
2009
Abstract Introduction The 5-HT 2A receptor is one of the most interesting targets within the serotonergic system because it is involved in a number of important physiological processes and diseases. Methods [ 18 F]MH.MZ, a 5-HT 2A antagonistic receptor ligand, is labeled by 18 F-fluoroalkylation of the corresponding desmethyl analogue MDL 105725 with 2-[ 18 F]fluoroethyltosylate ([ 18 F]FETos). In vitro binding experiments were performed to test selectivity toward a broad spectrum of neuroreceptors by radioligand binding assays. Moreover, first micro-positron emission tomography (μPET) experiments, ex vivo organ biodistribution, blood cell and protein binding and brain metabolism studies of…