ABSTRACT
The H2-receptor antagonists mifentidine, famotidine, cimetidine and ranitidine were examined for their ability to prevent the duodenal ulcer caused by mepirizole (250 mg/kg p.o.), a non-steroidal anti-inflammatory agent, in the conscious rat. All the compounds exerted a dose-related protective effect and on the basis of their ED50s, the following rank order of potency was found: mifentidine = famotidine greater than ranitidine greater than cimetidine. The antiulcer activity displayed by the H2-receptor antagonists evaluated in this model reflects their potency in inhibiting basal and stimulated gastric acid secretion in rat. The results of these studies indicate mifentidine as a potent anti-ulcer agent.
Subject(s)
Anti-Ulcer Agents , Duodenal Ulcer/prevention & control , Epirizole/antagonists & inhibitors , Histamine H2 Antagonists/pharmacology , Imidazoles/pharmacology , Pyrazoles/antagonists & inhibitors , Animals , Cimetidine/pharmacology , Dose-Response Relationship, Drug , Duodenal Ulcer/chemically induced , Duodenal Ulcer/pathology , Duodenum/pathology , Famotidine , Female , Intestinal Mucosa/pathology , Ranitidine/pharmacology , Rats , Rats, Inbred Strains , Thiazoles/pharmacologyABSTRACT
The binding characteristics of muscarinic receptors in rat salivary and lacrimal glands were studied by means of radioligand binding techniques. In competition experiments against [3H]N-methylscopolamine, classical muscarinic antagonists ipratropium bromide, N-methylscopolamine and N-methylatropine exhibited very similar KD values in all the glands and their binding behavior was well described by a one binding site model (nH congruent to 1). The novel cardioselective antimuscarinic compound, AF-DX 116, displayed an equally low affinity in all the tissues examined. Pirenzepine and dicyclomine, two other selective muscarinic antagonists, showed a similar behaviour in all but the sublingual gland, where their binding profile indicated the presence of a heterogeneous receptor population (nH = 0.74 and 0.84, respectively). Histological studies of the sublingual-submandibular glandular complex demonstrated the presence of ganglionic structures mainly located in the hilum of the sublingual-submandibular glandular complex connected with the sublingual gland. Binding studies carried out with pirenzepine on the hilum and on a synaptosomal preparation from this region again revealed the presence of two populations of muscarinic receptors with KD values of 22-25 and 270-463 nM. These results are best explained by the presence of M1 and M2 receptors located on neuronal and glandular structures.
