Niflumic acid, 2-{[3-(trifluoromethyl)phenyl]amino}pyridine-3-carboxylic acid (NFA), a nonsteroidal anti-inflammatory drug that blocks cyclooxygenase (COX), was shown previously to activate [Na(+)](i)-regulated Slo2.1 channels. In this study, we report that other fenamates, including flufenamic acid, mefenamic acid, tolfenamic acid, meclofenamic acid, and a phenyl acetic acid derivative, diclof...

In traditional molecular mechanics force fields, intramolecular non-bonded interactions are modelled as intermolecular interactions, and the form of the torsion potential is based on the conformational profiles of small organic molecules. We investigate how a separate model for the intramolecular forces in pharmaceuticals could be more realistic by analysing the low barrier to rotation of the p...

In addition to blocking cyclooxygenases, members of the fenamate group of nonsteroidal anti-inflammatory drugs have been proposed to affect brain GABAA receptors. Using quantitative autoradiography with GABAA receptor-associated ionophore ligand [35S]t-butylbicyclophosphorothionate (TBPS) on rat brain sections, one of the fenamates, niflumate, at micromolar concentration was found to potentiate...

Niflumic acid (NFA) is a member of the fenamate class of nonsteroidal anti-inflammatory drugs. This compound and its derivatives are used worldwide clinically for the relief of chronic and acute pain. NFA is also a commonly used blocker of voltage-gated chloride channels. Here we present evidence that NFA is an efficient blocker of chloride-permeable glycine receptors (GlyRs) with subunit heter...

line therapeutic agents for the treatment of arthritis. NSAID’s reduce the pain and swelling associated with arthritis by blocking the metabolism of arachidonic acid (AA) through the enzyme cyclooxygenase (COX) and thereby the production of prostaglandins, e.g. PGE2, which sensitizes nociceptors at nerve fiber terminals. Additionally, the 5-lipoxygenase (5-LO) products such as leukotriene B4 (L...

Calcium-activated chloride channels (ClCa) are crucial regulators of vascular tone by promoting a depolarizing influence on the resting membrane potential of vascular smooth muscle cells. Niflumic acid (NFA), a potent blocker of ClCa in vascular myocytes, was shown recently to cause inhibition and paradoxical stimulation of sustained calcium-activated chloride currents [ICl(Ca)] in rabbit pulmo...

Non-steroidal anti-inflammatory drugs (NSAIDs) are a common treatment for chronic inflammatory disorders but suffer from several unwanted side effects, particularly in the gastrointestinal (GI) tract. The GI-related side-effects can be reduced by masking of the carboxylate moiety of the NSAID, e.g., by chemical conversion into esters. Recently, it has been shown that activation of 7 nicotinic ...