RESUMO
These experiments investigated the effects of the new ACTH4-9 analog ebiratide (Hoe 427) [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH-(CH2)8-NH2 X 3 CH3COOH] on memory processes in mice and rats in five training tasks. With all five training and testing procedures (inhibitory avoidance test with ECS- or scopolamine-induced amnesia, up-hill avoidance, one-way shuttle box avoidance and eight-arm radial maze) ebiratide was most effective in a dose range of 1-10 micrograms/kg SC.
Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Aprendizagem da Esquiva/efeitos dos fármacos , Memória/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Hormônio Adrenocorticotrópico/farmacologia , Animais , Eletrochoque , Masculino , Camundongos , Camundongos Endogâmicos , Valores de Referência , Escopolamina/farmacologia , Isolamento SocialRESUMO
The ACTH4-9-analog Hoe 427 systemically injected in a dose range from 0.01-10 micrograms/kg caused a fall in acetylcholine (ACh) content in different brain areas of the rat. This effect occurred 0.5 hour after a single administration and lasted up to 24 hours. The decrease in ACh content induced by Hoe 427 was more pronounced when the animals were pretreated with dexamethasone (over 7 days 1 mg/kg SC, daily). Coadministration of the choline uptake inhibitor hemicholinium-3 (HC-3) and Hoe 427 potentiated the decrease in ACh content induced by HC-3. In the same dose range Hoe 427 acutely evoked an increase of the activity of the enzyme choline acetyltransferase as well as an elevation of brain cyclic GMP content. These data indicate that Hoe 427 enhances ACh metabolism in rat brain after systemic administration.
Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Encéfalo/metabolismo , Fragmentos de Peptídeos/farmacologia , Acetilcolina/metabolismo , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/administração & dosagem , Hormônio Adrenocorticotrópico/farmacologia , Aldosterona/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Colina O-Acetiltransferase/metabolismo , Corticosterona/metabolismo , GMP Cíclico/metabolismo , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Hemicolínio 3/farmacologia , Masculino , Especificidade de Órgãos , Oxotremorina/farmacologia , Fragmentos de Peptídeos/administração & dosagem , Ratos , Ratos Endogâmicos , Valores de Referência , Escopolamina/farmacologiaRESUMO
An open study was carried out in 12 male, healthy volunteers to investigate the renal tolerance of ofloxacin, a new, broad-spectrum oral antibacterial agent. Subjects received single doses of 300 mg and then repeated doses of 300 mg ofloxacin twice daily for 7 days. Urine was collected in several fractions during the study and the excretion of creatinine, alanine-aminopeptidase (AAP), gamma-glutamyl transferase (GGT) and n-acetyl-beta-glucose aminidase (NAG) was calculated in 12-hour fractions. Serum creatinine, beta 2-microglobulin concentrations and creatinine clearance were also determined. Based on the findings for the kidney enzymes AAP, GGT and NAG, renal tolerance was good. This was confirmed by creatinine clearance and serum beta 2-microglobulin values. Ofloxacin showed no nephrotoxic potential in this study.