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Biomedical subjects

G Bertaccini

Publications and source records attributed to G Bertaccini.

At least 109 records · Page 6Linked to original sources
PubMed1985

Characterization of cholinoreceptors in the rat urinary bladder by the use of agonists and antagonists of the cholinergic system.

The effects of stimulatory and inhibitory compounds acting on both nicotinic and muscarinic receptors have been evaluated in the isolated urinary bladder from adult and immature (14-18 days old) rats. Acetylcholine and bethanechol were found to induce concentration-dependent contractions which were inhibited by atropine and pirenzepine; compound McN-A-343 had a negligible contractile activity whereas DMPP had no effect at all. Responses to electrical field stimulation were abolished by tetrodotoxin (3 X 10(-8) M), enhanced by eserine (10(-8) M) and scarcely affected by hexamethonium (10(-3) M), trimethaphan (10(-3) M) and d-tubocurarine (10(-3) M). Atropine, pirenzepine and DMPP induced only a partial inhibition (50%) of the twitch response, whereas compound McN-A-343 caused a concentration-dependent inhibitory effect which was maximum (100% inhibition) at 10(-2) M. No significant differences were found between results obtained in immature and adult animals as regards either the stimulatory or the inhibitory compounds tested. It was concluded that postjunctional muscarinic receptors were responsible for the stimulatory responses observed, whereas an additional involvement of unknown mechanisms, probably not related to the cholinergic system, was suggested by the peculiar results obtained with DMPP and compound McN-A-343 on electrically-stimulated urinary bladder. Whatever the mechanisms involved, however, they are already present at the first stage of postnatal development.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1985

Effect of mifentidine on histamine-stimulated human atrium "in vitro": comparison with ranitidine and cimetidine.

The new H2-antagonist mifentidine was tested on human atrium, in comparison with cimetidine and ranitidine, for its activity against histamine-induced inotropic effect. Mifentidine was found to be 10 times more potent than ranitidine and 100 times more potent than cimetidine. The kinetics of the three compounds are typical of a competitive antagonism and the pA2 value was of 8.60, 6.35, 5.94 for mifentidine, ranitidine and cimetidine, respectively. Our data confirm previous findings in another isolated heart preparation, namely the guinea-pig papillary muscle.

Cimetidine↗
PubMed1985

Effect of the new H2-receptor antagonist mifentidine on gastric acid secretion in the cat: comparison with cimetidine and ranitidine.

The effect of the H2-receptor antagonist mifentidine (DA 4577) was studied in conscious fistula cats in comparison with cimetidine and ranitidine. Two series of experiments were carried out. In the first, submaximal gastric secretion was induced by continuous intravenous infusion of dimaprit (a selective H2-agonist). Once a plateau of gastric secretion had been reached, antagonists were infused intravenously at increasing doses for 3 hr. Mifentidine, ranitidine, cimetidine or saline were administered in different days at random order. In the second set of experiments, equiactive doses (that is the respective ED50s calculated from the previously established dose-response curves) of all the compounds were infused during dimaprit-induced acid hypersecretion, in order to evaluate their duration of action. All the compounds inhibited acid secretion in a dose-dependent fashion. Calculated ED50s were 0.39 +/- 0.05, 0.49 +/- 0.04 and 10.13 +/- 0.33 mumol.kg-1.hr-1 for mifentidine, ranitidine and cimetidine respectively. After the infusion of the equiactives doses, the half-life (that is the time taken to return to 50% inhibition) was 76.4 +/- 14.7 min for mifentidine, 38.3 +/- 10.1 min for ranitidine and 33.6 +/- 2.9 min for cimetidine. These data demonstrate that mifentidine is a potent antisecretory compound with a duration of action longer than that of cimetidine and ranitidine.

Animals↗
PubMed1984

Inhibition of gastric emptying and secretion by pirenzepine and atropine in rats.

The effects of pirenzepine and atropine on gastric emptying, gastric secretion and heart rate were studied in rats. Both drugs inhibited gastric emptying and secretion dose dependently and increased pulse rate. In the gastric secretory studies both compounds displayed potencies which were not very dissimilar (ID50 were 8.1 mumol X kg-1 and 1.4 mumol X kg-1 for pirenzepine and atropine respectively, potency ratio 6); pirenzepine was however decidedly less potent than atropine in inhibiting gastric emptying (potency ratio 36 on a molar basis) and in increasing heart rate (potency ratio 125). These data, in accordance with results of clinical trials, indicate that pirenzepine-unlike atropine-can inhibit acid secretion without appreciably affecting gastric motility and cardiac function.

Animals↗
PubMed1984

Action of the new H2-antagonist, DA 4577, on different in vitro and in vivo preparations.

The new H2-antagonist, 4(5)-(4- isopropylaminomethyleniminophenyl )-imidazole (compound marked DA 4577), was tested for its activity on different in vitro preparations and also in the conscious cat. Its effect was compared with that of some new H2 antagonists. Two sets of experiments were performed: in the first, concerning the specific H2-receptor antagonism, DA 4577 was found to be extremely potent on the guinea-pig papillary muscle and on the human atrium stimulated by histamine (pA2 = 8.24 and 8.60 respectively). Compound DA 4577 was also found very active in inhibiting histamine-induced acid secretion from the isolated rat fundus (pA2 = 7.37) and on the dimaprit-induced gastric secretion in conscious gastric fistula cats (ID50 = 0.39 mumol kg-1 h-1). In the second set of experiments, concerning effects independent of the H2-receptor blockade (side effects of the molecule), compound DA 4577 was found to be devoid of negative inotropic effect on the human atrium in the absence of histamine stimulation; in this respect it behaved like cimetidine or ranitidine but unlike oxmetidine which showed a constant negative inotropic effect even at concentration 10 times lower than those of DA 4577. Furthermore DA 4577 was ineffective in modifying gastrointestinal motility in vitro in concentrations up to 3 X 10(-4) M, conversely from ranitidine (which stimulated motility) and oxmetidine (which inhibited motility). On the whole DA 4577 appeared to be a very potent and selective H2 antagonist which, unlike other members of the family, is devoid of non-specific effect on human atrium and on motility of the gastrointestinal tract of different animal species.

Animals↗
PubMed1984

Action of histamine and of some H2-antagonists on gastric secretion 'in vitro'.

The effect of histamine and of some H2-antagonists on isolated gastric mucosal preparation from immature (14-18 days) rats, was investigated. Basal secretion varied, in our experimental conditions, between 1.06 and 3.54 mumol cm-2 h-1, reaching higher values (approximately 4.6 mumol cm-2 h-1) only in a small percentage of animals (10%). Histamine exerted a concentration-dependent stimulation of acid secretion in concentrations varying between 2 X 10(-6) and 1.6 X 10(-4) M. The response to histamine was competitively antagonized by ranitidine (pA2 value = 6.78) and by 4(5)-(4- isopropylaminomethyleniminophenyl ) imidazole (compound marked DA 4577) (pA2 value = 7.37). Oxmetidine acted as a competitive antagonist only for concentrations as low as 10(-8) M; higher concentrations (10(-7) and 10(-6) M) determined a non-competitive inhibition. Ranitidine and compound marked DA 4577 did not affect basal secretion up to concentrations of 3 X 10(-4) M. On the contrary oxmetidine exerted a concentration-dependent inhibition starting from 10(-5) M. Since in our experimental conditions the role of calcium ions in the regulation of basal secretion could not be established, the mechanism of action of oxmetidine was not completely clarified, even if an interference in the utilization of calcium ions may be suggested. In any case it is deemed of interest that this H2-antagonist was the only compound capable of inducing a reversible complete inhibition of basal acid secretion (only KSCN, in very high concentrations, had a similar behaviour).

Animals↗
PubMed1984

Action of mifentidine and ranitidine on the isolated rat uterus.

The new H2-antagonist mifentidine (compound marked DA 4577) was tested for its inhibitory effect on the relaxation induced by histamine on the rat uterus and was compared with the well known H2-blocker ranitidine. Mifentidine was shown to be more effective than ranitidine (about 10 times). However whereas ranitidine behaved as a "classical" competitive antagonist, mifentidine at concentrations of 10(-7) M, caused a remarkable depression of the maximum response to histamine. This "unsurmountable" antagonism may connected with a tight binding of the compound to the receptor with a consequent low degree of dissociation. Ranitidine, but not mifentidine, at concentrations of 10(-5) M was able to potentiate the stimulatory effect of acetylcholine thus confirming also in the uterus its cholinergic-like effects so far observed mainly in the gastrointestinal tract.

Acetylcholine↗
PubMed1984

Action of oxmetidine on the rabbit aorta: comparison with some calcium entry blockers and nitroglycerin.

The novel histamine H2 receptor antagonist, oxmetidine, was tested on isolated rabbit aorta for its activity on calcium ion transport and/or utilization suggested from previous experiments. Its effect was compared with that of some "classical" calcium entry blockers (verapamil, D-600 and nifedipine) and of nitroglycerin which acts predominantly on the intracellular calcium. The effect of all these compounds was evaluated against the contraction elicited by KCl, angiotensin and noradrenaline acting by different spasmogenic mechanisms. Oxmetidine was found to antagonize to approximately the same extent the effect of the three stimulatory substances: however concentrations required for this effect were from 10 to 100 times as high as those required to inhibit histamine H2 receptors. Nitroglycerin behaved quite similarly but was approximately 10.000 times more potent than oxmetidine. Verapamil and D-600 (which were virtually identical) were always more potent (about 10 times) than oxmetidine but less efficacious on the angiotensin-induced contraction. Finally nifedipine was the most active compound on the KCl induced contraction but was almost ineffective against angiotensin. It is concluded that oxmetidine, though with a still unclear mechanism, possesses a weak but definite inhibitory effect on the availability of the intracellular calcium resembling the effect of nitroglycerin. Whether or not an action on the influx of calcium is also present cannot be surely established as long as calcium fluxes are not measured. Differences in the behaviour of the "classical" calcium entry blockers suggest that each of them possesses, together with the main well recognized effect, additional effects responsible for apparently surprising results obtained against different spasmogenic compounds.

Animals↗
PubMed1984

Inhibition of the histamine-stimulated adenylate cyclase activity of guinea pig gastric cells by the H2-receptor antagonists cimetidine, oxmetidine and SKF 93479.

The effect of cimetidine and two new histamine H2-receptor antagonists, oxmetidine and SKF 93479, on histamine-stimulated adenylate cyclase activity was studied in guinea pig gastric mucosal cells. Histamine stimulated the enzyme activity in concentration-dependent fashion. The concentration-response curve of histamine was progressively shifted to the right in the presence of increasing concentrations of each antagonist. The Schild plot gave a straight line for all three compounds, with a slope not significantly different from unity and this suggested a competitive antagonism. The calculated pA2 values were 8.45 +/- 0.20, 7.73 +/- 0.21 and 6.81 +/- 0.15 for SKF 93479, oxmetidine and cimetidine, respectively. These results are in accordance with the pharmacological potencies of the antagonists reported on isolated heart preparation and on gastric secretion in vivo. Therefore, the inhibition of histamine-sensitive adenylate cyclase of gastric cells may represent an additional tool for the in vitro evaluation of the H2-receptor antagonists.

Adenylyl Cyclase Inhibitors↗
PubMed1984

Effect of ranitidine and cimetidine on gastric emptying of a mixed meal in man.

The effect of acute and chronic crossover administration of ranitidine and cimetidine on gastric emptying was studied in healthy volunteers and in duodenal ulcer patients, respectively. In the first series of experiments, intravenous ranitidine (50 mg) significantly (p less than 0.05) delayed emptying of both solids and liquids, whereas cimetidine (300 mg i.v.) was totally ineffective. In the second set of experiments, neither ranitidine (150 mg bd orally for two weeks) nor cimetidine (400 mg bd) significantly modified emptying rate. These results, therefore, suggest that only high blood levels of ranitidine, as elicited by intravenous administration, are able to affect gastric emptying. On the contrary, at steady state levels elicited by conventional therapeutic doses, no effect on gastric emptying is evident.

Administration, Oral↗
PubMed1984

Failure of somatostatin to inhibit the stimulatory effect of different compounds on the lower esophageal sphincter of the rat.

In the present paper the tetradecapeptide somatostatin was investigated for its possible inhibitory effect on the lower esophageal sphincter (LES) of the rat. Somatostatin, which is known to inhibit both release of several hormones and also their actions, was found to be ineffective on the isolated rat LES. The hormone did not inhibit basal tone and did not antagonize the stimulatory effect of different peptidic and non-peptidic biological substances. The meaning and the importance of the above observations are discussed.

Animals↗
PubMed1983

Impaired TSH response to TRH after intravenous ranitidine in man.

Ranitidine, given by i.v. infusion, decreased TSH response to TRH in 7 subjects. This effect, completely different from that obtained with cimetidine, suggests that the action of ranitidine is likely to be independent of H2-receptor blockade and rather may be related to the cholinergic-like effect of this drug.

Adult↗
PubMed1983

Effect of some new H2-receptor antagonists on gastrointestinal motility.

Some new histamine H2-receptor antagonists were tested for their effects on gastrointestinal motility. Ranitidine was found to possess definite stimulatory effects which appeared to be connected with an interference with the cholinergic system and occurred, though in different degree, from the lower esophageal sphincter (LES) to the colon. Etintidine, on the contrary, showed a remarkable antimuscarinic effect on the LES of the rat and the guinea-pig. Cimetidine, SK&F 93479 and tiotidine were virtually ineffective whereas oxmetidine exerted a consistent inhibitory activity on both basal motility and on the contractions induced by a variety of stimulatory agents. This effect, which was completely independent of the autonomic nervous system appeared to be connected with an inhibition of the transport of calcium ions. All the above results suggest that the H2-antagonists so far available may not be absolutely selective for the H2-receptor but may be endowed with non-specific effects which could have an interest at least from a pharmacological viewpoint.

Animals↗