RESUMO
We report the preparation of a series of eight L-alanyl-L-proline derivatives and four L-proline derivatives. Their pharmacological activity as antihypertensive agents was examined with reference to changes in the contractile response to angiotensin I (AI), bradykinine (BK) and angiotensin II (AII). Compounds 1g, 1h and 2c were the most powerful when compared with known angiotensin-converting inhibitors such as captopril and enalapril, and were selected for further pharmacological study.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/síntese química , Angiotensina I/farmacologia , Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacocinética , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Disponibilidade Biológica , Pressão Sanguínea/efeitos dos fármacos , Bradicinina/farmacologia , Captopril/farmacologia , Fenômenos Químicos , Química , Enalapril/farmacologia , Cobaias , Íleo/efeitos dos fármacos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Ratos , Ratos EndogâmicosRESUMO
The preparation of a series of 24 N-benzhydrylpiperazine derivatives is described. Their efficacy as calcium antagonists was examined with reference to changes in the permeability of the cell membrane to extracellular and intracellular calcium. Compounds 14, 15, 17 and 19 were the most powerful when compared with known calcium antagonists such as cinnarizine, flunarizine, and aligeron ([1-diphenylmethyl)-4-(2-propenyl)]-piperazine), and were selected for further study.
Assuntos
Compostos Benzidrílicos/síntese química , Bloqueadores dos Canais de Cálcio/síntese química , Piperazinas/síntese química , Animais , Aorta Torácica/efeitos dos fármacos , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/toxicidade , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/toxicidade , Fenômenos Químicos , Química , Hemodinâmica/efeitos dos fármacos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Norepinefrina/farmacologia , Piperazinas/farmacologia , Piperazinas/toxicidade , Cloreto de Potássio/farmacologia , Coelhos , Ratos , Relação Estrutura-Atividade , VasodilatadoresRESUMO
The influence of an acute treatment with cytidine diphosphate choline (CDP-choline, citicoline, Somazina) by intraduodenal route on cardiovascular and respiratory parameters in anesthetized rats is studied. No differences as compared with controls were observed in heart and respiratory rates. The values in arterial pressure and respiratory flow for CDP-choline groups were observed to be near the basal values. The inspiratory flow shows a statistically significant difference (approaching basal values) as compared with the decrease in controls.
