RESUMO
A series of 7-oxaaporphine derivatives was prepared. The compounds were evaluated as dopaminergic agents. None of them showed either affinity for dopamine receptors or activity in vivo in the climbing behavior (mice) and turning behavior (6-hydroxydopamine-lesioned rats) tests. The lack of activity is tentatively related to the effect of the oxygen atom on the pKa of these molecules.
Assuntos
Aporfinas/síntese química , Receptores Dopaminérgicos/efeitos dos fármacos , Animais , Aporfinas/metabolismo , Aporfinas/farmacologia , Comportamento Animal/efeitos dos fármacos , Fenômenos Químicos , Química , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Receptores Dopaminérgicos/fisiologia , Receptores de Dopamina D2 , Espectrofotometria Infravermelho , Relação Estrutura-AtividadeRESUMO
We have examined the adaptive modifications of brain monoamine receptors in response to pathophysiological processes in animal disease models: 6-OHDA lesioned and spontaneously hypertensive rats (SHR). The two models share a similar increase in D-1 receptor densities, while noradrenergic receptors are affected in different way: alpha-1 and beta are supersensitive in 6-OHDA lesioned rats and only alpha-2 are increased in SHR. S-1 receptors too are up-regulated in SHR. We must notice that though receptor hypersensitivity in the 6-OHDA model is linked to massive decreases in neurotransmitter levels, this mechanism seems not to exist in the SHR model.
Assuntos
Hipertensão/metabolismo , Doença de Parkinson Secundária/metabolismo , Receptores Adrenérgicos/metabolismo , Receptores Dopaminérgicos/metabolismo , Animais , Química Encefálica , Modelos Animais de Doenças , Dopamina/metabolismo , Hidroxidopaminas/toxicidade , Masculino , Norepinefrina/metabolismo , Oxidopamina , Doença de Parkinson Secundária/induzido quimicamente , Ratos , Ratos Endogâmicos SHR/metabolismo , Ratos Endogâmicos , Serotonina/metabolismoRESUMO
10-Methoxy-1,6-dimethyl-ergoline-8 beta-methanol-(5-bromonicotinate) (nicergoline, Sermion) shows a strong alpha-blocking activity both in vitro and in vivo. Various studies (dog, cat, rabbit, rat, mouse, guinea-pig) show that nicergoline affects only slightly blood pressure and heart rate and increases the blood flow in brain and hind limb without affecting the splanchnic and aortic flow in normal animals. Nicergoline does not interfere with CNS functions unless applied in high doses. It stimulates the muscle oxidative metabolism and function and lacks any emetic and hallucinogenic activity. Its acute and chronic toxicity in different animal species is very low.