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At least 19 recordsLinked to original sources

Influence of bethanechol on retained particles deposited on the first bifurcation of rabbits.

Retention of 4 micron 51Cr labelled Teflon particles administered to nine male rabbits via trachea was measured externally. About 5 microliter of a suspension with a particle concentration of 40 mg X ml-1 was deposited on the first bifurcation through a fiberoptic bronchoscope under urethane anesthesia. Over a period of two weeks, the rabbits were exposed twice, under the influence of the cholinergic drug bethanechol chloride and in a control examination. The time period during which 90% of deposited particles had cleared was significantly shorter in the presence of bethanechol (16 h) than in the control experiment (70 h). The magnitude of the fraction which cleared within the first hour did not differ significantly for drug administration and control, being 39.0% and 36.8%, respectively. The fraction which did not clear within the first hour tended (p = 0.1) to clear faster, half-time 10.4 h, when bethanechol chloride was given than it did in the controls, half-time 31.3 h. A reasonable interpretation of the results is that the cholinergic compound, bethanechol, increases bronchial secretion, which results in a reversed movement of the particles that previously penetrated the mucous layer, back to the mucous layer.

Animals

[Influence of a muscle relaxant, tizanidine, on gastric acid secretion and gastric ulcer in rats].

Effects of tizanidine, a centrally acting muscle relaxant, on gastric acid secretion and gastric ulcers were studied in the rat. Tizanidine (5 mg/kg, s.c.) did not influence basal acid secretion, but inhibited the centrally stimulated acid secretion in anesthetized rats. Intraduodenal administration of tizanidine (10 mg/kg) also inhibited the centrally stimulated acid secretion. The compound potentiated bethanechol-induced acid secretion at 10 mg/kg, s.c. Clonidine was found to have similar effects to tizanidine at the lower dose. Both tizanidine and clonidine inhibited basal acid secretion at a relatively low dose in conscious rats. Tizanidine (5 mg/kg, s.c.) did not modify indomethacin- and stress-induced ulcers, but Shay ulcers were slightly inhibited by the drug. Indomethacin ulcers were significantly inhibited by 10 mg/kg, s.c., 10 mg/kg, p.o. or 20 mg/kg, p.o. of tizanidine. Clonidine also was found to be a strong inhibitory agent of indomethacin-, stress- and Shay-ulcers. These results suggest that similar to clonidine, a high dosage of tizanidine influences gastric acid secretion and gastric ulcers, although the activity is lower than that of clonidine.

Anesthesia

Effects on gastric acid secretion of a steroidal alkaloid, epipachysamine-A, extracted from Pachysandra terminalis Sieb. et Zucc.

Effect of a steroidal alkaloid, epipachysamine-A, extracted from Pachysandra terminalis Sieb. et Zucc. on gastric acid secretion was studied in rats. Epipachysamine-A prevented 2-deoxy-D-glucose- or thyrotropin-releasing hormone-stimulated gastric acid secretion in anesthetized rats. However, the compound did not influence bethanechol- or electrical vagal stimulation-induced gastric acid secretion. These results suggest that the effect of epipachysamine-A is due to the influence on the central nervous regulatory mechanism in the gastric acid secretion.

Alkaloids

Effect of cimetropium bromide and other antispasmodic compounds on in vitro guinea-pig gallbladder.

The effect of cimetropium bromide, a new antimuscarinic compound, on bethanechol- and electrically-induced contractions was studied on isolated guinea-pig gallbladder. Atropine and two other widely employed antispasmodics (i.e., rociverine and octylonium bromide) were employed as reference compounds. Cimetropium and atropine proved to be competitive antimuscarinics, their pA2 being 7.77 +/- 0.14 and 8.31 +/- 0.14, respectively. On the contrary, rociverine displayed a dual effect being a competitive antagonist at low (up to 10(-5) mol/l) and a mixed one at high (greater than 10(-5) mol/l) concentrations. When tested against bethanechol- and electrically-induced contractions, all the compounds, with the exception of octylonium bromide, showed a concentration-dependent relaxant effect. In both experimental conditions, the potency of cimetropium was of the same order of magnitude as that of atropine and 150-200 times higher than that of rociverine. These data, together with the reported activity on human gallbladder in vivo and the well known involvement of cholinergic system in the control of gallbladder motility, could represent the rationale for the clinical use of cimetropium in the treatment of biliary colics as well as spasms of biliary tree.

Animals

Inhibition of gastric acid secretion in the dog by the H2-receptor antagonists, ranitidine, cimetidine, and metiamide.

The new H2-receptor antagonist, ranitidine, has been compared with cimetidine and metiamide as an inhibitor of gastric acid secretion in the dog. All three compounds were effective both intravenously or by mouth in inhibiting secretion induced by histamine, pentagastrin, or bethanechol. This inhibition was mainly attributable to a reduction in the volume of secretion, although there was also a significant reduction in the concentration of acid secreted. Metiamide was slightly less active than cimetidine, but ranitidine was four to nine times more potent than cimetidine, depending on the secretagogue used. The antisecretory activity of ranitidine does not result from a limitation in blood flow to the gastric mucosa.

Animals

Inhibitory effects of DF 594, a new antispasmodic agent, on intestinal motility in the dog.

DF 594, 11-(N-methylnipecotyl)-6,11-dihydro-5H-pyrido[2,3-b]-1,5-benzod iazepin-5-one hydrochloride, is a new antimuscarinic compound endowed with high affinity for intestinal muscarinic receptors and showing potent inhibitory effects on intestinal motility. This study investigated the intestinal motor effects of DF 594 in fasting, conscious dogs, chronically fitted with electrodes and strain gauges along the small bowel. In a first series of experiments, we assessed the antispasmodic activity of the compound by comparing the ability of intravenous DF 594 or atropine to antagonize the stimulatory effect of bethanechol (100 micrograms/kg s.c.). ED50 values for inhibition of bethanechol-stimulated contractions were 13.9 (8.8-21.8) and 4.0 (1.8-8.7) micrograms/kg for DF 594 and atropine, respectively. In a second series of experiments, we evaluated the effects of intravenous DF 594 and atropine on the migrating motor complex (MMC), monitoring heart rate as well. Similarly to atropine (30-100 micrograms/kg), DF 594 (100-300 micrograms/kg) blocked the further migration of an ongoing MMC and significantly delayed the onset of the following MMC. Unlike atropine, DF 594 had only a minor effect on heart rate at the highest dose tested (300 micrograms/kg). These data indicate that DF 594 is an effective antispasmodic agent at doses lower than those required to interfere with the MMC and is also less likely than atropine to induce cardiac side effects.

Animals

Action of different agonists and antagonists of the cholinergic system on the rat lower esophageal sphincter.

Several compounds acting on the cholinergic system at different levels were tested for their stimulatory or inhibitory effects on the isolated lower esophageal sphincter (LES) of the rat. Results obtained with acetylcholine, bethanechol and compound McN-A343 on the one hand and atropine, pirenzepine, ganglion blocking agents and tetrodotoxin on the other, suggested that LES contraction was associated mainly with the stimulation of post-synaptic muscarinic receptors. Nicotinic receptors (both ganglionic and muscular) seem to have a minor role, if any.

Animals

The effect of the new H2-receptor antagonist mifentidine on gastric secretion, gastric emptying and experimental gastric and duodenal ulcers in the rat: comparison with cimetidine and ranitidine.

The new H2-receptor antagonist mifentidine (DA 4577) was tested for its antisecretory and gastric motor effects in comparison with cimetidine and ranitidine. The Shay rat preparation (5 h) was used for studying gastric secretion; the gastric emptying of a liquid meal was chosen for studying gastric motility. All the three compounds inhibited acid secretion in a dose-dependent fashion. Calculated ED50s were 2.3, 12.2 and 92.8 mg X kg-1 for mifentidine, ranitidine and cimetidine, respectively. Therefore, in this animal model, mifentidine was about 40 times more potent than cimetidine and 5 times more potent than ranitidine. As far as gastric emptying is concerned, the effect of equiactive antisecretory doses (i.e. the respective ED50s calculated from the previously established dose-response curves) of all the three antagonists was completely different. Cimetidine delayed emptying rate, whereas ranitidine accelerated it and mifentidine was completely ineffective. However, at higher doses, also this compound affected emptying rate by reducing it dose-dependently. Gastric and duodenal ulcers were induced in the rat by dimaprit (100 mg X kg-1 intravenously) and cysteamine (250 mg X kg-1 subcutaneously), respectively. As far as gastric ulcer is concerned, the ED50s (the effective dose which protected 50% of the animals from lesions) were 0.23, 4.40 and 9.70 mg X kg-1 for mifentidine, ranitidine and cimetidine, respectively. As regards duodenal ulcer, the ED50 was 4.48 for mifentidine and 150.00 mg X kg-1 for ranitidine. In this animal model, the efficacy of cimetidine was very low. Therefore an ED50 could not be determined. In conclusion, results of the present investigation demonstrated that mifentidine is a potent antisecretory compound and an effective anti-ulcer agent in the rat.

Animals

Potentiation and inhibition of ganglionic transmission by ruthenium red.

The effect of ruthenium red, 2.5 to 5 muM, on ganglionic transmission in rat superior cervical ganglia and frog abdominal ganglia were studied in vitro. In rat ganglia, ruthenium red caused a spontaneous firing of ganglia cells, and an increase in the amplitude and duration of the compound action potential following a single stimulus volley. However, transmission following a conditioning volley or a repetitive stimulus train to the preganglionic nerve was depressed up to 60 sec. The asynchronous firing caused by bethanechol was potentiated by ruthenium red. In the frog, ruthenium red caused repetitive firing of ganglion neurons following either orthodromic or antidromic stimulation. It is suggested that the potentiation of the single potential and the spontaneous firing are due to a ruthenium red-induced increase in intracellular calcium concentration. The depression of transmission may be due to a temporary depletion of readily releasable acetylcholine. It is also suggested that ruthenium red has an effect on the postsynaptic membrane.

Action Potentials

Effects of membrane stabilizers on pancreatic amylase release.

Compounds with membrane stabilizing activity were studied as to their ability to affect pancreatic amylase release and the steps in the stimulus-secretion coupling process. Chlorpromazine, propranolol, and thymol were all found to inhibit bethanechol-stimulated amylase release and at slightly higher concentrations to induce release regardless of the presence of the secretagogue. This biphasic effect was similar to that found previously for the local anesthetic tetracaine. Release by high concentrations of propranolol and tetracaine was accompained by ultrastructural evidence of cell damage. Membrane stabilizers at concentrations which inhibited amylase release were shown to block bethanechol-induced depolarization and stimulation of 45Ca++ efflux although the drugs alone partially depolarized pancreatic cells. Release of amylase induced by Ca++ introduced by the ionophore A23187 was also abolished. The findings indicate that membrane stabilizers independently inhibit the steps leading to a rise in intracellular Ca++ and the subsequent Ca++-activated amylase release.

Amylases

Effect of omeprazole on gastric acid secretion by the rat isolated stomach.

The inhibitory effect of omeprazole has been investigated on the isolated gastric fundus from immature rats. Omeprazole (10(-7)-10(-5) M) inhibited basal acid secretion, conversely from H2-receptor antagonists, antimuscarinic compounds and calcium antagonists; the effect was mimicked only by KSCN (3 X 10(-4)-3 X 10(-2) M). Omeprazole (10(-6)-10(-5) M) caused an insurmountable antagonism of the hypersecretion induced by histamine and bethanechol, whereas it competitively antagonized the secretory response to isoprenaline and dibutyryl cAMP. Experiments carried out in low calcium media showed that calcium ions did not significantly affect the inhibitory potency of omeprazole when tested on basal acid secretion, whereas low calcium solutions enhanced the action of omeprazole against histamine-induced hypersecretion. The above data confirmed the potent antisecretory activity of omeprazole in different experimental conditions in which the common antisecretagogues are without effect and pointed out the novel site of action in the control of gastric acid secretion at intracellular level.

Animals

Gastric acid inhibitory action of a GABA-related compound, 3-amino-3-phenylpropionic acid, in the rat.

The acid inhibitory properties of 3-amino-3-phenylpropionic acid, a structural GABA analogue, were studied in the perfused rat stomach preparation. 3-Amino-3-phenylpropionic acid, 10 and 30 mg/kg i.v., dose dependently suppressed the gastric acid secretion induced by baclofen (2 mg/kg s.c.). This secretagogue action had been shown to be unaffected by either GABAA or GABAB receptor antagonists. The i.v. administration of 3-amino-3-phenylpropionic acid (3 and 10 mg/kg) was also effective to abolish the acid stimulatory effects of muscimol (1 mg/kg i.v.) and 2-deoxy-D-glucose (200 mg/kg i.v.). 3-Amino-3-phenylpropionic acid, even at the high dose (30 mg/kg i.v.) had no influence on the acid output in response to histamine and bethanechol. Furthermore, 3-amino-3-phenylpropionic acid had no significant effect on the acid secretion induced by electrical vagal stimulation. These results indicate that the antisecretory effect of 3-amino-3-phenylpropionic acid is different from those of antimuscarinics, H2-receptor antagonists and vagal blockade. Together, the results suggest that 3-amino-3-phenylpropionic acid might act in the brain to inhibit central regulation mechanisms of gastric acid secretion, probably through GABA mechanisms.

Animals

Hexocyclium derivatives with a high selectivity for smooth muscle muscarinic receptors.

1. The affinity of a number of derivatives of the muscarinic antagonist, hexocyclium, containing an amidine cationic head, for guinea-pig cardiac and ileal receptors was investigated. 2. All the compounds studied displayed a greater affinity for muscular than for cardiac muscarinic receptors. 3. The 5 fold ileal selectivity of hexocyclium was increased by a number of chemical substitutions. The largest discrimination between receptors (about 200 fold) was found for the formamidine derivative. 4. The selectivity displayed by the hexocyclium derivatives stemmed from a greater decrease in affinity towards cardiac as compared to ileal receptors.

Animals

[Effects of NIK-228 on gastric acid secretion in rats using the congo red sprayed method].

We have reported the antiulcer activities of a new compound that we named NIK-228 (3-hydroxy-methyl-2-methylimidazo [2, 1-b] benzothiazole). In the present report, we studied the antisecretory effects of NIK-228 on basal and stimulated gastric acid secretion using the Congo red sprayed method. Male Wistar rats (200 to 250 g) were used after 24 hr of fasting (without water). NIK-228, atropine and cimetidine were administered orally or intravenously 1 hr before operation for Congo red spraying. NIK-228 (100 mg/kg, p.o.), atropine (5 mg/kg p.o.) and cimetidine (100 mg/kg, p.o.) all inhibited basal gastric acid secretion. Oral administration of NIK-228 and atropine inhibited gastrin, 2-deoxy-D-glucose (2-DG) and bethanechol-induced acid secretion, but didn't inhibit histamine-induced acid secretion. Cimetidine inhibited all of histamine, gastrin, 2-DG and bethanechol-induced acid secretion. In vagotomized rats, oral and intravenous administration of atropine both inhibited bethanechol-induced acid secretion, but NIK-228 was not inhibited. These results suggested that antisecretory effects of NIK-228 were caused by the central vagal systems.

Animals

Acid-secretory effects of pentagastrin, histamine, urecholine, DBcAMP, and cBMP in isolated stomachs of fed and fasted rats.

Pentagastrin, histamine, urecholine, DBcAMP, and cGMP were all potent stimulants of acid secretion in the isolated stomach of the fed rat. With the exception of histamine and cGMP, all of these compounds were inactive when the stomach of the fasted rat was used. Pentagastrin was most effective when given on the serosal surface while histamine was equally potent whether it was added to the mucosal or serosal surface of the isolated stomach. The test would appear to be a relatively simply, but effective system for studying the basic mechanisms of action of several important secretagogues in the rat.

Animals