Phosphonate Derivatives of Paracetamol and Valproic Acid.

Paracetamol and valproic acid are standalone drugs with leading position in the world drug market. The phosphonate analogues of these drugs were synthesized and were tested in vivo. N-(4-hydroxyphenylcarbamoyl)phosphonic acid was four times more potent than paracetamol in preventing acetic acid-induced writhing.

Measuring sociability of mice using a novel three-chamber apparatus and algorithm of the LABORAS™ system.

Background: The social approach and social novelty tests utilizing the three-chamber apparatus are widely accepted to measure social behavior of rodents. The LABORAS™ system offers a possibility to assess sociability of mice in a reliable and objective manner.

New Method: We assessed the capability of the LABORAS™ sociability cage and algorithm (2.

Utility of different outcome measures for the nitroglycerin model of migraine in mice.

Introduction: Majority of the work for establishing nitroglycerin (NTG)-induced migraine models in animals was done in rats, though recently some studies in mice were also reported. Different special formulations of NTG were investigated in various studies; however, NTG treated groups were often compared to simple saline treated control groups. The aim of the present studies was to critically assess the utility of a panel of potential outcome measures in mice by revisiting previous findings and investigating endpoints that have not been tested in mice yet.

Effect of transient receptor potential vanilloid 1 (TRPV1) receptor antagonist compounds SB705498, BCTC and AMG9810 in rat models of thermal hyperalgesia measured with an increasing-temperature water bath.

The transient receptor potential vanilloid 1 (TRPV1) receptor is activated by noxious heat, various endogenous mediators and exogenous irritants. The aim of the present study was to compare three TRPV1 receptor antagonists (SB705498, BCTC and AMG9810) in rat models of heat hyperalgesia. The behavioural noxious heat threshold, defined as the lowest temperature evoking nocifensive reaction, was measured with an increasing-temperature water bath.

Chemical and biological investigation of N-hydroxy-valdecoxib: An active metabolite of valdecoxib.

The inhibition of cyclooxygenase enzymes plays an important role in the treatment of inflammatory diseases. N-Hydroxy-4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide (3)-a primary metabolite of the highly selective COX-2 inhibitor valdecoxib-was synthesized and stabilized as its monohydrate (3a.H(2)O).

New celecoxib derivatives as anti-inflammatory agents.

A series of 1,5-diarylpyrazoles with a substituted benzenesulfonamide moiety was synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities. Some compounds, for example, (+/-)-2-[4-(5- p-tolyl-3-trifluoromethyl-pyrazole-1-yl)-benzenesulfonylaminooxy]-propionic acid 16 and its disodium salt 21, had a higher in vivo anti-inflammatory activity compared to celecoxib, despite having no in vitro COX-1 or COX-2 inhibitory activity. Their gastrointestinal side effect profile is essentially more favorable than that of celecoxib.

Concerted action of antiepileptic and antidepressant agents to depress spinal neurotransmission: Possible use in the therapy of spasticity and chronic pain.

Chronic pain states and epilepsies are common therapeutic targets of voltage-gated sodium channel blockers. Inhibition of sodium channels results in central muscle relaxant activity as well. Selective serotonin reuptake inhibitors are also applied in the treatment of pain syndromes.

Nitrone derivatives of trolox as neuroprotective agents.

Synthesis of nitrone derivatives of trolox is described. Their biological evaluation was performed in vitro for scavenging different free radicals, inhibiting Fe(2+)-induced lipid peroxidation, and in vivo in a permanent middle cerebral artery occlusion model in mice. New compounds exert pharmacological activities comparable to or better than those of trolox or nitrone-type reference compounds.

Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits.

N-methyl-D-aspartate receptor (NMDAR) composition in granule cells changes characteristically during cerebellar development. To analyze the importance of NR2B replacement by NR2C and NR2A subunits until the end of the first month of age, we generated mice with lasting NR2B expression but deficiency for NR2C (NR2C-2B mice). Mutant phenotype was different from NR2C knock-out mice as loss of granule cells and morphological changes in NR2C/2B cerebellar architecture were already evident from the second postnatal week.