RESUMO
A series of 9H-xanthen-9-amines possessing a wide variety of nitrogen substituents at C-9 was prepared for evaluation of gastric antisecretory activity. These substituents included the acetamidine, imidate, pyrimidine, thiazoline, quinuclidine, 2-hydrazinopyridine, aminopiperidine, aminoalkylimidazole, and aminoalkylpyridine moieties. The majority of compounds in this series inhibited gastric acid secretion when tested orally in the pylorus-ligated rat. Potency was increased by intraduodenal administration and diminished by incubation with gastric juice, suggesting partial degradation of the compounds in the gastric environment. A representative example, 3-(9H-xanthen-9-ylamino)-1-ethylpiperidine, exhibited similar activity in dogs, although no free compound could be detected in the blood. It is therefore hypothesized that this compound is either rapidly bound to tissue and/or metabolized to an active species.
Assuntos
Ácido Gástrico/metabolismo , Xantenos/síntese química , Animais , Cães , Meia-Vida , Masculino , Pentagastrina/farmacologia , Ratos , Xantenos/farmacologiaRESUMO
Adverse reactions to cimetidine have been identified through the manufacturer's Worldwide Spontaneous Reporting System. Reactions not observed during clinical trials-mental confusion, interstitial nephritis, and potentiation of oral anticoagulants-were identified and added to the prescribing information for cimetidine while further studies were undertaken. The monitoring of the drug's adverse reaction profile is ongoing so that new types of reactions can be identified.
Assuntos
Cimetidina/efeitos adversos , Guanidinas/efeitos adversos , Cooperação Internacional , Anticoagulantes/farmacologia , Ensaios Clínicos como Assunto , Confusão/induzido quimicamente , Sinergismo Farmacológico , Humanos , Nefrite Intersticial/induzido quimicamente , Reino Unido , Estados UnidosRESUMO
A series of known antisecretory compounds, including glycopyrrolate, clonidine, propantheline bromide, CMN 131 (2-pyridylthiocetamide), and desmethylimipramine (DMI) were tested in the gastric fistula rat and monkey. The order of potency for inhibiting acid output was similar in both species. A general similarity exists in the responsiveness of the rat and monkey to gastric antisecretory agents. These data support the use of the squirrel monkey for assessment of gastric antisecretory activity.
