RESUMO
With the aim to split the pharmacological properties of lefetamine (CAS 14148-99-3), some structural modifications of this compound have been studied. The basic group of lefetamine has been shifted from the alkyl chain to the vicinal phenyl ring and the N-substitution has been changed. The dimethylaminomethyl derivatives and chiefly the o-morpholinometyhl exhibited a strong anti-visceral chemical antinociception activity stripped of thermal antinociception properties and physical dependence liability. Furthermore, through the introduction of a diethylaminomethyl group in the lefetamine structure some derivatives were selected exhibiting besided a significant increase in the anti-visceral chemical antinociception activity, remarkable local anesthetic properties.
Assuntos
Analgésicos não Narcóticos/síntese química , Analgésicos não Narcóticos/farmacologia , Anestésicos Locais/síntese química , Anestésicos Locais/farmacologia , Fenetilaminas/farmacologia , Analgésicos não Narcóticos/toxicidade , Anestesia Intravenosa , Anestésicos Locais/toxicidade , Animais , Anuros , Comportamento Animal/efeitos dos fármacos , Feminino , Cobaias , Dose Letal Mediana , Masculino , Camundongos , Medição da Dor/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Fenetilaminas/química , Fenetilaminas/toxicidade , Coelhos , Relação Estrutura-Atividade , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
The effects of glycine on morphine-induced antinociception were investigated in mice, using a cutaneous thermal test (hot-plate), a visceral chemical test (acetylcholine writhing test), and a locomotor activity test. When glycine (200 mg/kg p.o.) and morphine (5 mg/kg s.c.) were given together during the first 30 min, glycine first antagonized the morphine-induced antinociception then this was followed by a synergistic effect. The two-phase influence of glycine on morphine-induced antinociception may be due to the interaction of glycine with different receptors.
Assuntos
Analgésicos , Glicina/farmacologia , Morfina/farmacologia , Acetilcolina , Animais , Comportamento Animal/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Temperatura Alta , Camundongos , Morfina/antagonistas & inibidores , Atividade Motora , Dor/induzido quimicamenteRESUMO
The synthesis and the pharmacological properties of some new prazosin analogues are described.
Assuntos
Prazosina/análogos & derivados , Animais , Fenômenos Químicos , Química , Masculino , Camundongos , Prazosina/síntese química , Prazosina/toxicidade , Ratos , Ratos Endogâmicos SHRRESUMO
Organotin compounds have been studied for their biological properties, whereas very little is known about the effects of tin-inorganic derivatives on biological systems. Owing to our interest in the dithiocarbamate moiety in relation to metal redistribution in the body and to its biological import, we performed in vitro cytotoxicity experiments on dithiocarbamates. Preliminary results obtained with five tin-dithiocarbamates, where DDTC is the diethyldithiocarbamate anion, indicate some very promising compounds.
Assuntos
Ditiocarb/farmacologia , Estanho/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Camundongos , Microscopia Eletrônica de Varredura , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
The preparation of a number of prazosin-like derivatives is reported. The new derivatives differ from the parent compound for the 2-side-chain which is represented by peculiar fragments of butyrophenone neuroleptics. The results of the pharmacological evaluation are also reported.
Assuntos
Prazosina/análogos & derivados , Animais , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Químicos , Química , Feminino , Dose Letal Mediana , Camundongos , Prazosina/farmacologia , Prazosina/toxicidadeRESUMO
Esculetin determined a reduction in oedema and granulocyte infiltration in the Croton oil ear test in vivo. The drug was able to inhibit Acethylcholine-writhing test and showed a LD50 of 1450 mg/kg i.p. and greater than 2000 mg/kg by mouth. In our experimental conditions, esculetin has an anti-inflammatory and analgesic effect.
Assuntos
Anti-Inflamatórios não Esteroides , Umbeliferonas/farmacologia , Acetilcolina/toxicidade , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Óleo de Cróton/toxicidade , Avaliação Pré-Clínica de Medicamentos , Edema/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos , Peroxidases/metabolismo , Umbeliferonas/toxicidadeAssuntos
Guanetidina/farmacologia , Animais , Anuros , Guanetidina/análogos & derivados , Guanetidina/toxicidade , Cobaias , Masculino , Camundongos , Coelhos , Ratos , Ratos Endogâmicos SHRRESUMO
The acetylcholine writhing test and the hot plate test were used in mice to evaluate peripheral and central analgesia after porcine, salmon and human calcitonin administrations. ICV and IV injection of calcitonins caused a peripheral analgesia that persisted for at least 2 hr. SC injection of calcitonins did not produce peripheral analgesia. However, when administered by IP route, an increasing peripheral analgesia was observed. Although it had a slow onset, it was as powerful as after ICV or IV administration. Employing the hot plate test to determine the entity of a central analgesic response, the IP administration of calcitonin surprisingly revealed a hyperalgesic effect. It started soon after the injection, reaching its maximum after about 2 hr. At this point the hyperalgesic effects were fully antagonized by EDTA.2 Na ICV, or by Ca++ICV. Moreover only the latter produced a strong and long acting analgesia. Applying a central or peripheral test, calcium seems to play different roles on the algesia variations induced by calcitonins.
