Search results for "Aminopyridines"

Roflumilast, a phosphodiesterase 4 inhibitor, alleviates bleomycin-induced lung injury

2009

Mandarin translation of abstract Background and purpose:  The effects of a phosphodiesterase 4 (PDE4) inhibitor, roflumilast, on bleomycin-induced lung injury were explored in ‘preventive’ and ‘therapeutic’ protocols and compared with glucocorticoids. Experimental approach:  Roflumilast (1 and 5 mg·kg−1·d−1, p.o.) or dexamethasone (2.5 mg·kg−1·d−1, p.o.) was given to C57Bl/6J mice from day 1 to 14 (preventive) or day 7 to 21 (therapeutic) after intratracheal bleomycin (3.75 U·kg−1). In Wistar rats, roflumilast (1 mg·kg−1·d−1, p.o.) was compared with methylprednisolone (10 mg·kg−1·d−1, p.o.) from day 1 to 21 (preventive) or from day 10 to 21 (therapeutic), following intratracheal instillatio…

Inhalable Formulation Based on Lipid–Polymer Hybrid Nanoparticles for the Macrophage Targeted Delivery of Roflumilast

2022

Here, novel lipid-polymer hybrid nanoparticles (LPHNPs), targeted to lung macrophages, were realized as potential carriers for Roflumilast administration in the management of chronic obstructive pulmonary disease (COPD). To achieve this, Roflumilast-loaded fluorescent polymeric nanoparticles, based on a polyaspartamide-polycaprolactone graft copolymer, and lipid vesicles, made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-distearoyl-sn-glycero-phosphoethanolamine-N-(polyethylene glycol)-mannose, were properly combined using a two-step method, successfully obtaining Roflumilast-loaded hybrid fluorescent nanoparticles (Man-LPHFNPs@Roflumilast). These exhibit colloidal size and a ne…

The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease

2009

After more than two decades of research into phosphodiesterase 4 (PDE4) inhibitors, roflumilast (3-cyclopropylmethoxy-4-difluoromethoxy-N-[3,5-di-chloropyrid-4-yl]-benzamide) may become the first agent in this class to be approved for patient treatment worldwide. Within the PDE family of 11 known isoenzymes, roflumilast is selective for PDE4, showing balanced selectivity for subtypes A-D, and is of high subnanomolar potency. The active principle of roflumilast in man is its dichloropyridyl N-oxide metabolite, which has similar potency as a PDE4 inhibitor as the parent compound. The long half-life and high potency of this metabolite allows for once-daily, oral administration of a single, 500…

Roflumilast for asthma: Weighing the evidence

2015

Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.

2013

Respiratory syncytial virus (RSV) causes acute exacerbations in COPD and asthma. RSV infects bronchial epithelial cells (HBE) that trigger RSV associated lung pathology. This study explores whether the phosphodiesterase 4 (PDE4) inhibitor Roflumilast N-oxide (RNO), alters RSV infection of well-differentiated HBE (WD-HBE) in vitro. WD-HBE were RSV infected in the presence or absence of RNO (0.1-100 nM). Viral infection (staining of F and G proteins, nucleoprotein RNA level), mRNA of ICAM-1, ciliated cell markers (digital high speed videomicroscopy, β-tubulin immunofluorescence, Foxj1 and Dnai2 mRNA), Goblet cells (PAS), mRNA of MUC5AC and CLCA1, mRNA and protein level of IL-13, IL-6, IL-8, T…

Antihyperalgesic and analgesic properties of the N-methyl-d-aspartate (NMDA) receptor antagonist neramexane in a human surrogate model of neurogenic …

2006

Abstract NMDA-receptors are a major target in the prevention and treatment of hyperalgesic pain states in neuropathic pain. However, previous studies revealed equivocal results depending on study design and efficacy parameters. We tested the analgesic (generalized reduction of generation and processing of nociceptive signalling) and anti-hyperalgesic (prevention of central sensitization) properties of the NMDA-receptor antagonist neramexane and the potassium channel opener flupirtine in the intradermal capsaicin injection model. Furthermore, we tested the effect on pain summation (wind up). Eighteen healthy subjects received either a single dose of neramexane (40 mg p.o.), flupirtine (100 m…

Repeated exposure of fluazinam fungicides affects gene expression profiles yet carries no costs on a nontarget pest

2021

Fungicides are used to control pathogenic fungi of crop species, but they have also been shown to alter behavioral, life history and fitness related traits of non-target insects. Here, we tested the fungicide effects on feeding behavior, survival and physiology of the non-target pest insect, the Colorado potato beetle (Leptinotarsa decemlineata). Feeding behavior was studied by a choice test of adult beetles, which were allowed to choose between a control and a fungicide (fluazinam) treated potato leaf. Larval survival was recorded after 24-hour and 72-hour exposure to control and fungicide-treated leaves with two different concentrations. The adults did not show fungicide avoidance behavio…

4-Aminopyridine antagonizes the inhibitory effect of pentobarbital on acetylcholine release in the heart

1980

Effects of pentobarbital on acetylcholine (ACh) release, force of contraction and nervous conduction were studied in isolated heart preparations and in cervical vagus nerves, respectively. 4-Aminopyridine and tetracaine were used as pharmacological tools to eludicate the mode of action of pentobarbital. 1. 4-Aminopyridine (10−4 M) markedly increased the overflow of ACh from the isolated chicken heart evoked by electrical stimulation (1–50 Hz, 1 ms, 40 V) of the cervical vagus nerves. This effect of 4-aminopyridine was highest at low frequencies of stimulation (+ 226% at 1 Hz) and declined with increasing frequencies to reach a minimum augmentation of 22% at 30 Hz. 2. Pentobarbital and tetra…

EFFECTS OF 4-AMINOPYRIDINE ON ACETYLCHOLINE OUTPUT FROM THE CEREBRAL CORTEX OF THE RAT in vivo

1982

Abstract 1 The effects of 4-aminopyridine (4AP) on the output of acetylcholine (ACh) from the cerebral cortex were investigated in unanaesthetized freely moving rats and in anaesthetized rats by means of the `cup technique'. ACh was determined by bioassay on the dorsal muscle of the leech. 2 In unanaesthetized rats intraperitoneal injection of 4AP (3 mg/kg) had no effect on the cortical output of ACh. 3 After injection of morphine (10 mg/kg s.c.), which depressed the spontaneous output of ACh, 4AP increased the cortical output to a level significantly higher than that determined before morphine injection. 4 In rats anaesthetized with either urethane or pentobarbitone, drugs known to decreas…

Self-Organization of 2-Acylaminopyridines in the Solid State and in Solution

2010

Aggregation of 2-acylaminopyridines and their 6-methyl derivatives in chloroform solution was studied by (1)H, (13)C, and (15)N NMR spectroscopies. The results were compared with (13)C and (15)N CPMAS NMR and IR spectral as well as with X-ray structural data. Intermolecular interactions in solution and in solid state were found to have a similar nature. Relatively strong N(amide)-H···N(pyridine) intermolecular hydrogen bonds enable dimerization to take place. Steric interactions in N-pivaloyl- and N-1-adamantylcarbonyl as well as that caused by the 6-methyl group hinder formation of the dimeric aggregates stabilized by the N(amide)-H···N(pyridine) intermolecular hydrogen bonds. In general, …