Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety.

Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented.

Nitrate reduction to ammonia: a dissimilatory process in Enterobacter amnigenus.

Thirty-four bacterial isolates from an agricultural soil anaerobically preincubated in the presence of glucose were tested for their ability to reduce nitrate to ammonia or to denitrify in two different media: nitrate broth and a minimal medium enriched with glucose. Ten isolates were considered denitrifying bacteria and 7 were dissimilatory ammonia producers. Ammonia production by the isolate identified as Enterobacter amnigenus was quantified and attained 50% of 138 mg∙L(-1) of added NO(3)(-) N. The dissimilatory character of this reduction was clearly confirmed by culturing this (15)N-labeled bacterium in the presence of unlabeled nitrite. Nitrous oxide was produced at the same time as nitrite was reduced to ammonia. Increasing nitrate N levels from 48 to 553 mg∙L(-1) in culture medium resulted in an increase in the level of nitrite produced and simultaneously a decrease in ammonia and nitrous oxide production. Key words: dissimilatory nitrate reduction, dissimilatory ammonia production, denitrification, Enterobacter amnigenus, (15)N.

Dissimilatory ammonia production vs. denitrification in vitro and in inoculated agricultural soil samples.

A dissimilatory ammonia-producing isolate identified as Enterobacter amnigenus and a denitrifier identified as Agrobacterium radiobacter isolated from the same soil were studied. The products of nitrate reduction in a minimal medium, enriched with glucose and containing nitrate N as the sole nitrogen source, were quantified when each of these isolates was cultured anaerobically, alone or mixed together in the presence or absence of C(2)H(2). When they were cultured together, ammonia was the principal product of nitrate reduction. The distribution between denitrification and dissimilatory ammonia production (DAP) for nonsterilised soil samples inoculated with E. amnigenus or A. radiobacter, or a mixture of these two isolates, was also investigated. Production of NH(4)(+) was increased under these conditions (strict anaerobiosis and much available fermentable carbon), but the inoculation of soil samples with 1.2 × 10(7) cells of E. amnigenus·g dried soil(-1) was not sufficient to shift nitrate reduction from nitrous oxide (denitrification) to ammonia production, suggesting that inoculation with a greater number of DAP bacteria than introduced would probably be required to enable ammonia production to exceed nitrous oxide release. Key words: dissimilatory ammonia production, denitrification, Enterobacter amnigenus, Agrobacterium radiobacter.