The bronchoconstrictor action of the tetradecapeptide bombesin in the guinea-pig

The tetradecapeptide bombesin was found to exert a potent spasmogenic action on the bronchiolar muscle of the anaesthetized guinea-pig. The threshold bronchoconstrictor dose ranged between 50 and 200 ng kg^?1. Other spasmogenic substances tested in the same experimental conditions, except physalaemin, were much less effective. Since antagonists of acetylcholine, histamine or 5-hydroxytryptamine did not inhibit the bronchoconstriction it is suggested that bombesin acts either by direct stimulation of the smooth muscle or by the prior release of other, as yet unidentified, spasmogenic substances.     

Synthesis and anti-inflammatory, antipyretic and analgesics properties of 5-(1,2-benzisothiazolyl)tetrazoles

Tetrazole analogs of a series of known 1,2-benzisothiazolalkanoic acids were synthesized and tested for anti-inflammatory, antipyretic and analgesic activities in comparison with their corresponding carboxylic acids. The benzisothiazoliltetrazoles showed high antipyretic activity and each tetrazole, except one, was appreciably more potent than the corresponding acid. The examined tetrazoles are generally inactive as anti-inflammatory agents and weakly active in the mouse writhing test, with effect comparable with those of the corresponding carboxylic acids.     

H2-antagonists: synthesis and activity of 2-amino-5-thiazolyl derivatives

2-Amino- and 2-guanidinothiazole derivatives having in position 5 a methylthioalkyl side-chain with urea-equivalent moieties were prepared for comparison with H2-antagonists of cimetidine and tiotidine series. Examination of the pharmacological results obtained from experiments on guinea pig atria and in cat gastric fistula, suggests some general observations about the structure-activity relationship of the compounds synthesized. The activity trend of these products is different from that of H2-imidazole antagonists while it is similar to that of the tiotidine series. Unlike the tiotidine similar compounds, the 2-guanidino-5-thiazolyl derivatives are less potent than the corresponding 2-amino-5-thiazolyl products. The activity of the latter ones is reduced in comparison to that of tiotidine or cimetidine.     

Pharmacological profile of new thioperamide derivatives at histamine peripheral H1-, H2-, H3-receptors in guinea-pig

The recent availability of potent and selective ligands, namely R-()-methylhistamine and thioperamide, led to conclusive progresses as regards histamine H₃-receptor knowledge. The aim of this work is to investigate byin vitro tests the pharmacological properties of new amino and methyl derivatives of the H₃-antagonist thioperamide. Such original compounds, developed by the modulation of the thioperamide imidazolyl moiety, were assayed at guinea-pig ileal contractile H₁-, atrial chronotropic H₂- and enteric neuronal H₃-receptors.None of the drugs exhibited interaction with H₁ or H₂ sites. On electrically stimulated ileum, two of the thioperamide methyl derivatives competitively antagonized the inhibitory effect of the H₃-agonist R-()-methylhistamine. On the basis of the Schild analysis, the more active isomer (compound IV) displayed an affinity at H₃-receptors only five times lower than thioperamide. These results could contribute to elucidate further the structural features required to develop potent and selective H₃-antagonists. On the other hand, to prove the hypothesized apparent heterogeneity between peripheral and central H₃-sites, as emerged by pharmacological and binding studies, autoradiographic investigations are in progress.