Disposition and activity in experimental allergic encephalomyelitis of flumizole, a nonacidic, nonsteroidal, anti-inflammatory agent

The nonacidic, nonsteroidal, anti-inflammatory agent, flumizole, penetrates the central nervous system of rats following oral drug administration, reaching concentrations in brain and spinal cord which are several-fold higher than plasma concentrations. Maximum drug concentrations in brain and plasma are achieved simultaneously and decay with similar half-lives (8 h). The drug is well absorbed orally and is excreted primarily with feces after biliary secretion. The distribution and elimination of flumizole is comparable in normal rats and in rats afflicted with experimental allergic encephalomyelitis; the drug is not selectively concentrated at either peripheral or central nervous system sites of inflammation. Flumizole is inactive in the rat model of the disorder under conditions that demonstrate therapeutic success with myelin basic protein.     

Clobazam and diazepam in anxiety

The anxiolytic effects of clobazam, diazepam, and placebo were compared in a 4-wk double-blind study of 159 anxious outpatients, primarily from family practice. Clobazam (30 to 80 mg/day) and diazepam (15 to 40 mg/day) were found to induce similar side effect, primarily sedation, and although both active drugs induced greater clinical improvement than placebo, clobazam induced the largest degree of improvement in most aspects. It was speculated that the relatively high daily dosage of diazepam may have been contributed to these results.     

Site of intestinal dipeptide hydrolysis

1. Sacs of everted small intestine of the hamster have been used to study the site of final hydrolysis of twelve dipeptides. 2. The results suggest that L-alanyl-glycine, glycyl-glycine, L-valyl-L-valine, L-alanyl-L-valine, L-valyl-L-alanine and L-prolyl-glycine are hydrolysed beyond the locus of the active transport mechanism for D-glucose, perhaps even within the cell. These may be designated class 1 (deep) dipeptides. 3. In contrast, superficial (perhaps even surface) hydrolysis seems to occur with L-alanyl-L-alanine, L-leucly-L-leucine, glycyl-L-alanine, L-alanyl-L-leucine, L-leucyl-L-alanine and glycyl-L-proline. These may be designated class 2 (superficial) dipeptides. 4. All the dipeptides were able to partially inhibit D-glucose active transport, the findings supporting the view that more than one mechanism may exist for the active absorption of the sugar.