Although the need for sound research on the outcome of mental disease has long been recognized, and although probably no other medical specialty has accumulated such an abundance of statistics as psychiatry, yet the dearth of adequately designed investigations especially in the field of the evaluation of therapy is conspicuous. The literature describing and appraising the results of insulin, me...

The antiseizure activity of benzodiazepines (BDZs) 1-5 in mice and rats as animal models is described. These BDZs have selective efficacy for alpha2beta3gamma2 and alpha3beta3gamma2 GABA(A)-receptors. Significant anticonvulsant activity with little or no motor impairment and therapeutic indexes (TI) of 2.8-44 (mice, ip) were observed for compounds 2-4 in the subcutaneous metrazole seizure (scME...

As a continuation of our study on a number of 1,3-substituted pyrrolidine-2,5-diones, in this paper we report the synthesis, physicochemical and anticonvulsant properties of new derivatives of N-4-arylpiperazin-1-yl amides of (2-aza-1,3-dioxospiro[4.5]dec-2-yl)-acetic acid. The amides [II-X] were prepared by condensation of the formerly obtained (2-aza-1,3-dioxospiro[4.5]dec-2-yl)-acetic acid [...

A series of novel stereochemically pure derivatives of the investigative broad-spectrum anticonvulsant ADD408003 was designed and synthesized. Five-center four-component (U-5C-4CR) and four-center three-component (U-4C-3CR) variants of Ugi reaction were used in the key step of the synthetic pathways. The compounds obtained were evaluated for the anticonvulsant activitiy in the maximal electrosh...

Administration of the convulsants pentylenetetrazole (Metrazole) or picrotoxin to rats caused a dramatic increase in mRNAs of four putative transcription factor genes, zif/268, c-jun, jun-B, and c-fos, in neurons of the hippocampus and dentate gyrus, as well as other areas of the cerebral cortex, including pyriform cortex and cingulate cortex. The increase in these mRNAs was rapid and transient...

Effects of repeated postnatal administration of caffeine (10 and 20mg/kg s.c. daily from P7 to P11) were studied in two models of epileptic seizures characterized by spike-and-wave EEG rhythm in 18- and 25-day-old rats. Rhythmic metrazol activity (RMA, model of human absences) was induced by low dose of pentylenetetrazol (PTZ, 20mg/kg or 40mg/kg, i.p.) and minimal clonic seizures (model of huma...

BACKGROUND Postnatal treatment with caffeine from P7 to P11 (10 or 20 mg/kg daily) resulted in transient changes in two pentylenetetrazole (PTZ)-induced models of epileptic seizures characterized by spike-and-wave EEG rhythm in immature rats. To know if some changes persist into adulthood we studied these models in young adult Wistar rats. METHODS Caffeine treatment at a daily dose of 10 and/...