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81.
De Amici M Conti P Fasoli E Barocelli E Ballabeni V Bertoni S Impicciatore M Roth BL Ernsberger P De Micheli C 《Il Farmaco; edizione pratica》2003,58(9):739-748
A set of novel heterocyclic ligands (7a-9a, 7b-9b, and 9c) structurally related to oxotremorine 2 was designed, synthesized, and tested at muscarinic receptor subtypes. In the binding experiments at cloned hm1-5, the presence of the 2-methylimidazole/2-methyl-3-alkylimidazolium moiety in place of the pyrrolidine ring revealed, in derivatives 8a, 8b, and 9c, a moderate selectivity for some receptor subtypes. The functional in vitro assays yielded results that correlated closely to binding data. In general, on passing from agonists bearing the pyrrolidine moiety to their analogues carrying the 2-methylimidazole function, the overall pharmacological efficacy profile is shifted from agonism toward partial agonism. The insertion of the 2-methyl-3-alkylimidazolium moiety advances the effect such that the compounds are pure antagonists. Quite similarly, chiral 3-oxo-Delta(2)-isoxazoline (+/-)-10 behaved as a weak antagonist unable to discriminate the different muscarinic receptor subtypes. 相似文献
82.
M Impicciatore G Morini M Chiavarini E Barocelli F Bordi P V Plazzi F Vitali 《Agents and actions》1987,20(3-4):262-264
A representative group of 2-aminothiazolylethylamine derivatives, in which the gastric acid secretion stimulating S-aminoalkylisothiourea moiety can be recognized, was tested. The quite different responses observed suggest that in vivo but not in vitro some events mimicking an H2-receptor agonist-like activity rather than a direct interaction with H2-receptors could take place. On the basis of structure-activity relationships, it can be speculated that the active conformation of dimaprit is not that resembled by these compounds which have been considered as cyclic models of one of its possible conformations. 相似文献
83.
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. 相似文献
84.
Prof. M. Impicciatore G. Morini M. Chiavarini P. V. Plazzi F. Bordi F. Vitali 《Inflammation research》1986,18(1-2):134-136
The pharmacological properties of 2-aminohistamine and 2-amino-5-methylhistamine were studied and compared with those of histamine, 5-methylhistamine and dimaprit. The introduction of an amino group in position 2 of the histamine imidazole ring caused a reduction of histamine potency, mostly with respect to H1 receptors. Such disactivation was much more evident in its corresponding 5-methyl derivative. The pharmacological activity related to the chemical structure will be discussed in the paper. 相似文献
85.
1. Bombesin stimulated acid secretion from the denervated fundic pouch of the dog. Whereas the concentration of hydrochloric acid in bombesin-produced juice was always higher than in control juice this did not occur for pepsin, the concentration of which remained below the basal values. The threshold dose of bombesin was 5-30 ng/kg by the subcutaneous route and 0·05-0·2 (μg/kg)/h by intravenous infusion. At low doses bombesin was more active than caerulein, even on a molar basis, and at high dose levels was as active as caerulein. In contrast to gastrin and caerulein, bombesin elicited a moderate secretory response also following rapid intravenous injection.
2. The acid secretion provoked by bombesin was almost completely inhibited by atropine and reduced by approximately 50% by hexamethonium.
3. Bombesin did not stimulate acid secretion in the lumen-perfused preparation of the rat stomach when administered by subcutaneous injection (up to 10 μg/kg) or by intravenous infusion (up to 10 (μg/kg)/hour). An irregular increase in acid output was observed only following rapid intravenous injection and this was of doubtful significance.
4. The mechanism of the secretagogue action of bombesin on the dog stomach is discussed.
相似文献86.
F Bordi M Mor P V Plazzi C Silva G Morini M Impicciatore E Barocelli M Chiavarini 《Il Farmaco; edizione pratica》1992,47(5):551-565
Continuing their studies on benzisothiazolyl derivatives, Authors refer to the preparation and pharmacological properties of 4-(1,2-benzisothiazol-3-yl) alkanoic and phenylalkanoic acids. All substances were tested for anti-inflammatory, analgesic and antipyretic properties. As reference compounds, 1,2-benzisothiazolin-3-one and 4-(3-oxo-1,2-benzisothiazolin-3-yl) phenylacetic acid, as prototypes of benzisothiazolinonic derivation. Ibuprofen, as a prototype of substituted arylalkanoic acids, and Phenylbutazone were used. Analysis of the data leaded to the following conclusions. Introduction of the aryl moiety, passing from benzisothiazolylalkanoic to benzisothiazolyl-phenylalkanoic structures, produced a remarkable increase of activity. 2-[4-(1,2-benzisothiazol-3-yl)phenyl] propionic and 2-[4-(1,2-benzisothiazol-3-yl)phenyl]butyiric acids showed anti-inflammatory, analgesic and antipyretic properties comparable to those of Ibuprofen. Substantial differences in variations in activities were observed comparing the properties of benzisothiazolylphenylalcanoic acids with those of the benzisothiazolinonic series, object of preceding studies. 相似文献
87.
Carrying on the study of the effects induced by substitution at position 2- of histamine imidazole ring, this article briefly reports the synthesis of 2-(2-oxo-4-imidazolin-4-yl)ethylamine. The pharmacological properties of this compound and its sulphurated analogue 2-(2-thiono-4-imidazolin-4-yl)ethylamine, showed that the marked structural modification of the critical moieties involved in the binding at the H1- and H2-receptors resulted in a loss of histamine-like activity. 相似文献
88.
G Morini M Chiavarini E Barocelli M Impicciatore 《Pharmacological research communications》1988,20(11):949-961
Different doses of the new chemically stable PGE2 analogue, FCE 20700, (150, 300, 450, 900, 1200 and 1800 micrograms kg-1) and of 16,16-dimethyl PGE2, DMPGE2, (1, 3, 10, 30 and 100 micrograms kg-1) were administered by gavage to pylorus-ligated rats. The dose-response relationship in preventing gastric mucosal damage and in inhibiting gastric acid and pepsin secretion was investigated. In the same animals, a simultaneous evaluation of barrier and luminal mucus was also performed. Both compounds were markedly active in preventing the macroscopic damage of the gastric mucosa and, at higher doses, in inhibiting gastric acid secretion. FCE 20700 was approximately 100-150 times less potent than DMPGE2. Mucosal protection appeared to be exerted by the two prostaglandins independently of any action on mucus. Furthermore, as the antisecretory doses were approached, a decline in protective activity became evident, suggesting that the dosage of prostaglandins is critical, making it possible to orient their activity either towards mucosal protection or towards acid inhibition. 相似文献
89.
H2-receptor but not H1-receptor antagonists, administered by intravenous infusion, produce a dose-dependent constriction of superior mesenteric arterioles of the anaesthetized rat under resting conditions. However the possibility that this effect could be related to a blockade of H2 receptors is unlikely, since their potency on blood flow changes does not parallel known H2-receptor antagonist activity. Furthermore, the estimated potency ratio is not in the expected order if the vasoconstriction is due to H2-antagonism, the potency ratios on guinea-pig atrial muscle and on mouse gastric acid secretion being famotidine greater than oxmetidine greater than ranitidine greater than cimetidine. 相似文献
90.
Interaction of selective compounds with muscarinic receptors at dispersed intestinal smooth muscle cells. 总被引:2,自引:2,他引:0
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E. Barocelli M. Chiavarini V. Ballabeni F. Bordi M. Impicciatore 《British journal of pharmacology》1993,108(2):393-397
1. The characterization of muscarinic receptors on single cells of the guinea-pig ileum longitudinal smooth muscle, devoid of neuronal elements, was functionally studied by estimating the affinities of muscarinic antagonists on acetylcholine-induced contractions. 2. Atropine (5 x 10(-11) to 5 x 10(-6) M), 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP, 5 x 10(-8) to 5 x 10(-6) M), cyclohexyl(4-fluoro-phenyl) (3-piperidinopropyl) silanol (pFHHSiD, 5 x 10(-7) to 5 x 10(-5) M) as well as pirenzepine (5 x 10(-7) to 5 x 10(-5) M) competitively antagonized the acetylcholine-dependent contractions with different affinities (atropine > 4-DAMP > pFHHSiD > pirenzepine). 3. Methoctramine (5 x 10(-7) to 5 x 10(-5) M), and AF-DX 116 (5 x 10(-6) and 5 x 10(-5) M) also showed antagonist properties but these deviated from simple competition. These compounds, which discriminate between M2 and M3 receptors, showed a potency lower than that of pirenzepine, the rank order of potencies being pirenzepine > methoctramine > AF-DX 116. When concentrations of AF-DX 116, methoctramine and pirenzepine were increased an unspecific contractile effect occurred. 4. McN-A-343, a partial agonist on intact guinea-pig longitudinal smooth muscle strips, on this preparation induced a weak contraction (about 7% in comparison to control) that was not reversed by antimuscarinic agents. 5. These data indicate that M3 rather than M2 receptor sites are present on this tissue. 相似文献