Assuntos
Antagonistas Adrenérgicos beta/história , Etanolaminas/história , Propranolol/história , Antagonistas Adrenérgicos beta/farmacocinética , Antagonistas Adrenérgicos beta/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Gatos , Cães , Etanolaminas/farmacocinética , Etanolaminas/farmacologia , Cobaias , Meia-Vida , Coração/efeitos dos fármacos , História do Século XX , Dose Letal Mediana , Propranolol/farmacocinética , Propranolol/farmacologia , CoelhosAssuntos
Guanidinas/farmacologia , Imidazóis/farmacologia , Receptores Histamínicos H2/efeitos dos fármacos , Receptores Histamínicos/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Cães , Suco Gástrico/metabolismo , Cobaias , Frequência Cardíaca/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
The concept of two classes of histamine receptor, H1 and H2, is introduced and the chemical derivation of histamine H2-receptor antagonists is outlined briefly. Starting from the structure of histamine, chemical modification led eventually to burimamide, the first described histamine H2-receptor antagonist. Further stepwise modifications ultimately afforded metiamide and cimetidine. In vitro studies show that cimetidine is a specific competitive histamine H2-receptor antagonist. In vivo, it is a potent inhibitor of histamine-stimulated gastric acid secretion in rats and dogs after both intravenous and oral administration. It is equally potent as an inhibitor of pentagastrin-stimulated secretion. The evidence suggests that cimetidine inhibits gastric acid secretion through blockade of histamine H2-receptors in the gastric mucosa. Cimetidine has been shown to have low acute toxicity. Repeated dose studies of up to 24 months in rats and up to 12 months in dogs have been carried out and the results are presented and discussed. There is no known toxic effect which would limit the usefulness of cimetidine in man.
Assuntos
Cimetidina/farmacologia , Guanidinas/farmacologia , Antagonistas de Androgênios , Animais , Fenômenos Químicos , Química , Cimetidina/administração & dosagem , Cimetidina/metabolismo , Cães , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Suco Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Cobaias , Antagonistas dos Receptores H2 da Histamina , Cinética , Dose Letal Mediana , Masculino , RatosRESUMO
Burimamide and metiamide are two histamine H2-receptor antagonists. Evidence is presented that indicates the competitive nature and the specificity of the antagonism. Metiamide is about ten times more potent than burimamide and is also more effective than burimamide when given orally. Both compounds inhibit gastric secretion and the evidence is consistent with this inhibition being due to competitive antagonism of H2 receptors in the gastric mucosa. Burimamide, unlike metiamide, causes release of catecholamines even at dose levels that are just sufficient to produce H2-receptor antagonism. Burimamide, but not metiamide, has alpha-adrenoceptor blocking activity. In certain models for inflammation, particularly rat paw edema induced by compound 48/80, burimamide in combination with the H1-receptor antagonist mepyramine shows anti-inflammatory activity. This may, in part, be associated with the catecholamine-releasing properties of the compound. Metiamide is less active in this respect.
Assuntos
Burimamida/farmacologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Histamina/metabolismo , Metiamida/farmacologia , Receptores de Droga , Tioureia/análogos & derivados , Animais , Anti-Inflamatórios , Catecolaminas/metabolismo , Cães , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Cobaias , Contração Muscular/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Ratos , Receptores de Droga/efeitos dos fármacos , Útero/efeitos dos fármacosRESUMO
Cimetidine, a new H2-receptor antagonist, was safely administered to eighteen healthy man by the intravenous, intraduodenal or oral route. 2 When gastric secretion was maximally stimulated by either histamine or pentagastrin, the simultaneous administration of cimetidine produced marked inhibition of both acid and pepsin secretion. 3 Cimetidine was well absorbed by mouth and had a blood half-life of 2 hours. 4 Cimetidine was rapidly excreted via the kidneys and about 70% of the excreted material was unchanged drug. 5 Clinical evaluation of cimetidine in patients with peptic ulceration is recommended.