ABSTRACT
The dopamine agonist bromocriptine and L-dopa significantly inhibited whereas dopamine antagonist haloperidol aggravated the gastric lesions induced by pylorus ligation in mice as found earlier for rats. Furthermore, the successful use of a dopamine antagonist alone for the induction of gastric lesions also in mice was demonstrated, since the gastric lesions were induced by a single dose of haloperidol without any additional noxious treatment. Bromocriptine successfully inhibited both the gastric lesion-potentiating as well as the gastric lesion-inducing effect of haloperidol.
Subject(s)
Bromocriptine/toxicity , Dopamine Antagonists , Haloperidol/toxicity , Levodopa/toxicity , Pylorus/drug effects , Stomach Ulcer/chemically induced , Animals , Female , Male , Mice , Mice, Inbred C3HABSTRACT
Gastric lesions were provoked in all rats that had received intraperitoneally a single dose of the dopamine antagonists haloperidol, metoclopramide or domperidone 24 h before. Dose-dependence was demonstrated for haloperidol. This drug induced gastric lesions as early as 90 min after its application. The ulcerogenic effect of haloperidol was completely prevented or markedly reduced by simultaneous applications of dopamine agonists bromocriptine or L-dopa. We conclude that the model of gastric lesions induced by dopamine antagonists could be successfully applied in further investigations of the role of dopamine in the pathogenesis of ulcer disease.
Subject(s)
Dopamine Antagonists , Stomach Ulcer/chemically induced , Animals , Bromocriptine/pharmacology , Domperidone/pharmacology , Female , Haloperidol/pharmacology , Levodopa/pharmacology , Male , Metoclopramide/pharmacology , Rats , Rats, Inbred StrainsABSTRACT
beta-Hydroxytryptamine and beta-hydroxy-5-hydroxytryptamine were incubated with rat liver slices and oxidative deamination was established as the main route of metabolism: in both instances the corresponding indole-3-glycollic acids and indole-3-ethane diols were the major metabolites. However, the rates of deamination of beta-hydroxylated tryptamines, as measured manometrically, were found to be much slower than those of tryptamines nonhydroxylated in the side chain. The pharmacological activities of beta-hydroxylated tryptamines were tested in guinea-pigs on resistance of respiratory pathways, spontaneous respiration, electrocardiogram, blood pressure and isolated ileum, using tryptamine and 5-HT as reference substances. The effects of tryptamines hydroxylated in the side chain were in general similar to those of corresponding tryptamines but of much lower intensities; only in increasing the blood pressure was beta-hydroxytryptamine as active as tryptamine. The different reactions of these two groups of substances in the presence of some antagonists indicate that the receptors are probably not the same.
