Action of caerulein and related substances on the pyloric sphincter of the anaesthetized rat

The effects of caerulein and related substances on the gastro-duodenal junction of the anaesthetized rat were examined by means of three different techniques. Caerulein appeared to be endowed with a potent spasmogenic action on the pyloric sphincter; the threshold dose was as low as 1–5 ng/kg. The C-terminal octapeptide of cholecystokinin was approximately half as active. Desulphated caerulein retained only 1% of the activity of the mother substance, pentagastrin was twice as active as desulphated caerulein. Secretin had a noticeable spasmogenic activity whereas prostaglandin E₁ showed a remarkable spasmolytic effect against the pyloric contraction elicited by caerulein. Results obtained with parasympatholytic and sympatholytic drugs suggested that the activity of caerulein is a ‘direct’ one independent of the autonomic nervous system.     

The anti-H1-histaminic and antimuscarinic effect of 2- and 4-[benzyl-(2-dimethylaminoethyl)amino]pyrimidine compounds

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).     

Inhibitory effect of intracranial injections of tachykinins on angiotensin-induced drinking in the cat

The tachykinins eledoisin, substance P and kassinin were administered by pulse intracerebroventricular (ICV) injections to cats made thirsty by ICV angiotensin II, 100 ng per cat. Eledoisin, 100 ng per cat, produced an inhibition of drinking which was larger (56.0 vs. 45.2%) and lasted longer than that evoked by 400 ng per cat of substance P. Kassinin, 100 ng per cat, did not evoke any effect at all. The treatment with these peptides neither produced signs of discomfort nor induced any other behavioural alteration. The results of present experiments suggest that the antidipsogenic effect of tachykinins is a phenomenon of general interest among mammals.     

Pharmacological characterization of H3 receptor antagonists with imidazole,thioimidazole and thioimidazoline polar groups in the side chain

Inflammation Research -     

Imidazole H-2 agonists. Synthesis and activity of 2-(2-amino-4-imidazolyl)ethylamine (2-aminohistamine) dihydrochloride

The syntheses of 2-(2-amino-4-imidazolyl)ethylamine (2-aminohistamine) dihydrochloride and of the corresponding 5-methyl derivative are described. The histamine-like properties of the two salts are tested in vitro on isolated ileum and gastric fundus of guinea-pig. The results are discussed and compared with those of other H2-agonists.     

Antagonistic properties of N-methyl-N'-[2-(5-ethyl-4-imidazolyl-methylthio)ethyl]thiourea.

In the present paper the Authors describe the synthesis and the biological effects of N-methyl-N'-[2-(5-ethyl-4-imidazolylmethylthio)ethyl]thiourea (etiamide). This compound appeared to inhibit, to a certain extent, the effect of histamine on H2-receptors. This inhibition, however, was less pronounced than that elicited by metiamide and in some of the preparations examined appeared to be of the non-competitive type.     

3-Benzyl-1,2-benzoisothiazoles: spasmolytic properties of the aminoalkyl derivatives

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.