RESUMEN
N-Substituted 5-aminomethylquinoxalinediones containing carboxy or phosphonic acids yield potent and selective AMPA and/or NMDA (glycine-binding site) antagonists. Phosphonic acid derivatives are particularly water-soluble and display potent anticonvulsant effects in the electroshock-induced convulsion assay in mice.
Asunto(s)
N-Metilaspartato/antagonistas & inhibidores , Organofosfonatos/farmacología , Quinoxalinas/síntesis química , Quinoxalinas/farmacología , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/antagonistas & inhibidores , Aminoácidos/química , Animales , Modelos Animales de Enfermedad , Electrochoque , Ácido Bromhídrico/farmacología , Ácido Clorhídrico/farmacología , Hidroxiácidos/química , Concentración 50 Inhibidora , Ratones , Organofosfonatos/químicaRESUMEN
A series of 5-aminomethylquinoxaline-2,3-diones have been identified as potent and selective AMPA antagonists. Some of these compounds are also active at the glycine-binding site of the NMDA receptors. A number of these novel, water-soluble quinoxaline-2,3-dione derivatives display protective effects in the electroshock-induced convulsion model in mice.
Asunto(s)
Antagonistas de Aminoácidos Excitadores/farmacología , Quinoxalinas/farmacología , Receptores AMPA/antagonistas & inhibidores , Animales , Antagonistas de Aminoácidos Excitadores/química , Ratones , Quinoxalinas/química , Convulsiones/prevención & controlRESUMEN
Potent antagonists at the glycine-binding site of NMDA receptors, as well as dual antagonists acting also at AMPA receptors have been identified in a series of 5-arylaminomethylquinoxaline-2,3-diones. A study of the structure-activity relationship of these compounds is reported here.
Asunto(s)
Antagonistas de Aminoácidos Excitadores/farmacología , Glicina/metabolismo , Quinoxalinas/farmacología , Receptores AMPA/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Antagonistas de Aminoácidos Excitadores/química , Antagonistas de Aminoácidos Excitadores/metabolismo , Quinoxalinas/química , Quinoxalinas/metabolismo , Receptores de N-Metil-D-Aspartato/química , Relación Estructura-ActividadRESUMEN
The exposure of surface dressing workers to polycyclic aromatic hydrocarbons (PAH) was studied. Four different paving sites, at which coal tar-containing binders were applied, were selected as work sites with high exposure levels of PAH. Breathing zone airborne particulates, contamination of the skin with PAH, and 1-hydroxypyrene in urine of the workers involved in chip sealing were determined. Substantial concentrations of cyclohexane-soluble airborne particulate matter were found (GM = 0.2 mg/m3, n = 28). Skin contamination was determined using two different methods: with exposure pads and by hand washing. Pads were mounted on several parts of the body: wrist, elbow, neck, shoulder, and ankle. The pads located on the wrist appeared to be the most contaminated (pyrene: GM = 22 ng/1.77 cm2, n = 40). The end-of-shift hand washing showed that the hands of the workers were contaminated with PAH (pyrene: GM = 70 micrograms, n = 35). Preshift hand washing showed far lower, but detectable, quantities of PAH on workers' hands (pyrene: GM = 5 micrograms, n = 35). Enhanced levels of urinary 1-hydroxypyrene among the workers were found. The highest levels were found in the end-of-shift urine samples. Correlations between the pyrene exposure variables were studied. Significant positive correlations were found between pyrene on the wrist pad versus end-of-shift urinary 1-hydroxypyrene; between pyrene on the hands versus end-of-shift urinary 1-hydroxypyrene; and between the two different skin contamination variables.