Search

The influence of fentonium, a new derivative of hyoscyamine, on the gastric secretion has been evaluated in rats, cats and dogs. The compound appeared to be able to markedly reduce the gastric hypersecretion produced by pentagastrin, caerulein and bethanechol; its antagonizing activity against histamine stimulation was poor.

A new series of 3-methoxy-1,2-benzisothiazol-5-ylacetic acid analogs and some of their functional derivatives were synthesized and tested for their analgesic, antipyretic and anti-inflammatory activities. From an analysis of the relationship between structure and pharmacological activity, it was observed that modifications in the acid group induced useful variations in the parameters studied.

The synthesis and chemical and pharmacological properties of 3-benzyl-1,2-benzisothiazoleaminoalkyl derivatives are reported. These compounds were studied because 4-dimethyl-2-phenyl-2-(1,2-benzisotiazol-3-yl)-butyramide and N,N-dimethyl-3-phenyl-3-(1,2-benzisothiazol-3-yl)propylamine were recently found to have antispasmodic properties. Most of the compounds studied aspecifically inhibited the contracturant effects of acetylcholine, histamine and BaCl2. Three of them showed mixed antagonism (competitive and non-competitive) versus acetylcholine and histamine, showing both antimuscarinic and antihistaminic properties. However the antimuscarinic action prevailed over the others, as shown by pA2 and pD'2 calculated values. On the basis of the results obtained, the structure-activity relationships is discussed.

This paper reports the synthesis of 2- and 4- [benzyl-(2-dimethylaminoethyl)amino]pyrimidine compounds and the evaluation of their inhibitory properties against histamine (H1), acetylcholine and barium chloride, on guinea pig isolated ileum. 4-[p.Methoxybenzyl-(2-dimethylaminoethyl)amino]-2-methoxy-pyrimidine (VIII) is shown to possess H1 receptor antagonist activity, with a potency similar to that observed for Tonzylamine. By contrast, a specific, although weak, antimuscarinic effect is displayed by 4-[benzyl-(2-dimethylaminoethyl)amino]-2-methoxy-5-methylthio-pyrimidine (XII).

This paper describes the synthesis of 3-benzyl-1,2-benzisothiazole derivatives, structurally related to benzylisoquinolines, and their analgesic activity studied using writhing technique in the mouse. The presence of lipophilic substituents in position 3, 4 of the benzyl group give substances with analgesic activity, although their "potency" is lower than that shown by papaverine.

This paper describes the synthesis of 2- and 4-[benzyl-(2-dimethylaminoethyl)amino]pyrimidine compounds and their antihistaminic properties studied on isolated guinea-pig ileum. Calculated pA2 values show that the antihistaminic activity of 4-[p.methoxybenzyl-(2-dimethylaminoethyl)amino]pyrimidine is specific and potent (8-10 times higher than that of thonzylamine).

The synthesis of a new series of 4-(3-oxo-1,2-benzisothiazolin-2-yl)phenylalkanoic compounds and some of their functional derivatives is described. The compounds, on the basis of data obtained from 1,2-benzisothiazolin-3-one derivatives, were biologically examined mainly for their antiphlogistic and analgesic actions. Results obtained, in analyzing the relationship between structure and pharmacological actions, suggest that both 4-(3-oxo-1,2-benzisothiazolin-2-yl)-phenyalkanoic acids and o-sulphobenzimido alkanoic esters are endowed with pain-killing effects comparable in potency and efficacy with phenylbutazone.

As a part of a study on H2-agonists, the preparations and properties are reported for a representative group of 2-aminothiazolethylamine derivatives which contain the gastric secretion stimulating S-aminoalkylisothiourea moiety. The test compounds were obtained by known methods or from 2-(2-amino-5-thiazolyl)ethyl chloride and were tested for their possible histamine-like activities on different biological substrates. From the biological results it appears that the behaviour of the substances is rather complex, but the following general observations can be pointed out: the contracturant properties, sometimes quite marked, do not derive from direct H1-specific activities; the effects, particularly evident in stimulating in vitro or in vivo gastric secretion, in relaxing gall-bladder smooth muscle, on auriculae and/or on blood pressure, are not competitively antagonized by cimetidine; none of the tested compounds proved to be an antagonist of histamine H2-receptors, while one of them is found to inhibit competitively the H1-receptors. On the basis of structure-activity relationships it can be excluded that the iuxta-nuclear NH2 group of 2-aminothiazolethylamines reacts, in some way, with the H2-receptors, since, in this case, the 2-aminothiazole group is not a pharmacophore like the 2-aminoimidazole or isothiurea group. Consequently the hypotheses, that the flexibility of the molecule is a fundamental requirement for the H2-stimulating properties of S-(3-dimethylaminopropyl)isothiurea and that the different activities of 2-aminohistamine, in comparison with those of 2-methylhistamine, are due to the existence of a hydrophilic area suitable for the allocation of the iuxta-nuclear NH2 group in the H2-receptor, are strengthened.

The effects of some imidazole derivatives, H2-antagonists and H2-agonists, with different alkyl groups in 5-position (R = Me, Et, i.Pr), were studied comparatively on cat gastric secretion and guinea-pig gastric fundus. The antagonistic and agonistic activities decrease with increase in the substituent inductive effect, and, in particular, it should be noted that the cimetidine ethyl analog (compound V) is a competitive antagonist of H2-histamine receptors. More hypotheses on the H1- and H2-receptor surfaces are proposed.

Two series of experiments were performed on rat chronic ulcer in order to assess the possible curative and mucosal protective properties of 2 week treatments, or the preventive properties of 4 week treatments with antisecretory agents, acting with different mechanisms of action. At the end of the treatments the gastric secretory and motor responsiveness to a gastrin-like stimulus was simultaneously evaluated. The results support the view that antimuscarinic agents as well as H2-blockers cannot be defined as protective and that after a 4 week treatment they can induce modifications of gastric functions.