piperidines and timepidium-bromide

We report a patient who presented with multiple small submucosal nodules with granulomatous inflammation in the minor salivary glands of the oral cavity. A 43-year-old woman presented with a 1-week history of multiple small submucosal nodules in her oral cavity after having taken medicine for abdominal pain. The patient did not have a history of fever, rectal bleeding, skin lesions or arthritis, but did have a history of drug allergy and bronchial asthma. Histopathological examination of the submucosal nodules showed sialadenitis with marked infiltration of lymphocytes, eosinophilic cells, macrophages and Langhans-type or foreign-body-type multinucleate giant cells. The macrophages tended to be aggregated and appeared to have caused immature granuloma formation without caseous necrosis. Degranulated eosinophilic cells were numerous. Sarcoidosis, Crohn's disease, tuberculosis and atypical mycobacterial infection were not identified by medical examination. Three weeks after discontinuing the medication the patient was seen again at a follow-up visit. Multiple submucosal small nodules and other symptoms were not evident at that time. This case report may represent a new entity of salivary gland disease that we tentatively refer to as 'allergic granulomatous sialadenitis'.

Topics: Abdominal Pain; Adult; Anti-Ulcer Agents; Diagnosis, Differential; Enzymes; Female; Granuloma; Humans; Hypersensitivity; Inflammation; Liver Diseases; Piperidines; Ranitidine; Salivary Glands, Minor; Sialadenitis

Topics: Allopurinol; Eosinophilia; Female; Folliculitis; Gout Suppressants; Humans; Middle Aged; Piperidines; Suppuration

Topics: Animals; Cisapride; Colon; Domperidone; Gastrointestinal Motility; Humans; Male; Metoclopramide; Piperidines; Pressure; Rats; Rats, Inbred Strains

An effective and selective procedure for the extraction of ambenonium chloride (AMBC) from serum using a weak cation-exchange extraction cartridge has been developed. The solid-phase extraction procedure permitted the extraction of AMBC from serum without adhesion to materials such as the containers. A 200-microliter volume of the eluate could be directly injected on to a reversed-phase ion-pair high-performance liquid chromatographic column. The recovery was in the range 97-100%. The limit of detection for AMBC was 0.5 ng/ml in serum (signal-to-noise ratio = 3). The method was used to determine the serum concentration of AMBC in patients with myasthenia gravis. The method would be useful for monitoring AMBC in serum in order to study its pharmacokinetic behaviour in patients under oral administration therapy.

Topics: Adult; Ambenonium Chloride; Chemical Phenomena; Chemistry; Chromatography, Ion Exchange; Female; Humans; Male; Middle Aged; Myasthenia Gravis; Piperidines; Spectrophotometry, Ultraviolet

The intracholedochal pressure changes induced by timepidium bromide were studied in 12 patients who had undergone surgery because of gall bladder stones and were receiving transient external bile drainage by the Kehr method. Cholangiomanometric examination, carried out under basal conditions and after an intravenous dose of 15 mg timepidium bromide, revealed a statistically significant decrease in mean intracholedochal pressure in all 12 patients. It is concluded that timepidium bromide is likely to exert a direct action on the sphincter of Oddi, decreasing its basal tone and thus causing a decrease in intracholedochal pressure.

Topics: Aged; Ampulla of Vater; Drug Evaluation; Female; Humans; Male; Manometry; Middle Aged; Piperidines; Sphincter of Oddi

The effect of the antispasmodic agent, SA-504 subtle granules, was studied. Ninety mg per day of timepidium bromide subtle granules was given orally to 17 patients with renal or ureteral calculi for no less than fourteen days. SA-504 subtle granules as well as the capsule showed good antispasmodic effect and stimulated spontaneous passage of ureteral calculi. No subjective or objective side effects were observed.

Topics: Adolescent; Adult; Aged; Dosage Forms; Female; Humans; Kidney Calculi; Male; Middle Aged; Parasympatholytics; Piperidines; Ureteral Calculi

Effects of timepidium bromide (TB; anticholinergic agent), acetylcholine (ACh) and neostigmine (Neost) on gastric and duodenal blood flow distribution were studied by the use of 131I-labeled macroaggregated human serum albumin (MAA) in rabbits. In normal rabbits, gastric blood flow was found to be uneven in various regions of the stomach: anterior corpus (50% of total gastric blood flow) greater than posterior corpus (40%) greater than pyloric antrum (7%). Intravenous administration of TB (200 microgram/kg) to normal rabbits produced a slight increase in total gastric blood flow, but the increase in the mucosal layer of the pyloric antrum was considerable. On the other hand, ACh (10 microgram/kg, i.v.) and Neost (50 microgram/kg. i.v.) significantly reduced the total gastric blood flow, in particular, the mucosal blood flow in the anterior and posterior corpus. This reduction in blood flow was virtually abolished by TB and was restored to the normal level. These results suggest that these cholinergic or anticholinergic drugs affect the gastric blood flow and that these effects may be mediated through muscarinic receptors. Blood flow in the duodenum was only slightly changed by these drugs.

Topics: Acetylcholine; Animals; Autoradiography; Duodenum; Male; Neostigmine; Parasympatholytics; Piperidines; Rabbits; Regional Blood Flow; Serum Albumin, Radio-Iodinated; Stomach

As quaternary ammonium compounds are generally not absorbed from gastric mucosa, the direct action of these compounds on the gastric mucosa can be investigated by means of intragastric (oral) administration to pylorus ligated animals. Effects of timepidium bromide (TB), an anti-cholinergic quaternary ammonium compound, on gastric secretion of pylorus ligated rats were investigated. When TB (100 mg/Kg) was administered orally, the secretion volume of gastric juice decreased slightly, while the concentrations of free acid and pepsin in gastric juice decreased remarkably. When TB was administered intraduodenally (100 mg/kg) or subcutaneously (10 mg/kg), secretion of gastric juice and free acid was strongly inhibited, but the pepsin concentration in gastric juice was not influenced (i.d.) or slightly increased (s.c.). In the oral administration of various drugs such as atropine, hyoscine-N-butylbromide and oxethazaine (Ox), only Ox caused a decrease in pepsin concentration in gastric juice. Similar effects of TB on the pepsin concentration in the gastric juice were also observed in experiments using stomach perfused rats. TB has no effect on enzymatic activity of pepsin in in vitro experiments. From these results, it is assumed that TB inhibits acid and pepsin secretion mainly by a direct action on the gastric mucosa.

Topics: Animals; Depression, Chemical; Gastric Mucosa; Ligation; Male; Parasympatholytics; Pepsin A; Piperidines; Rats; Rats, Inbred Strains; Thiophenes

Effects of timepidium bromide (TB), hyoscine-N-butylbromide (HB) and atropine (Atr) were studied on the isolated guinea pig gallbladder and sphincter of Oddi. In the isolated gallbladder, the contraction induced by methacholine was competitively antagonized with TB, HB and Atr: pA2 values for TB, HB and Atr were 8.44, 7.55 and 9.11, respectively. Contraction of gallbladder after field stimulation at 5 Hz was also inhibited by TB, HB and Atr as well as by tetrodotoxin (TTX). On the other hand, TB had no significant influence on the electrically evoked (30 Hz) contraction which remained after treatment with TTX. It was estimated that the inhibitory activity of TB on the contraction of gallbladder was 1/5-1/6 that of Atr and 7 times as potent as HB. In the isolated sphincter of Oddi, TB, HB and Atr reduced the perfusion pressure increased by acetylcholine (ACh), the activity of TB being 1/4 that of Atr and 3 times of HB. The contractile responses to field stimulation (5 Hz) were also inhibited by TB, HB and Atr. The inhibitory activity of TB was 1/5 that of Atr and 12 times of HB. It was also demonstrated that TB produced no significant effect on the noradrenaline (Nor)-induced contraction and isoproterenol (Iso)-induced relaxation in the gallbladder or Nor-induced increase of the perfusion pressure in the sphincter of Oddi. It is suggested that TB acts on the gallbladder and sphincter of Oddi by virtue of its anticholinergic activity.

Topics: Acetylcholine; Ampulla of Vater; Animals; Atropine; Butylscopolammonium Bromide; Depression, Chemical; Electric Stimulation; Gallbladder; Guinea Pigs; In Vitro Techniques; Male; Methacholine Compounds; Muscle Contraction; Muscle, Smooth; Norepinephrine; Parasympatholytics; Perfusion; Piperidines; Scopolamine Derivatives; Sphincter of Oddi; Thiophenes

Effects of timepidium bromide (TB) on the motility of various smooth muscles and the secretion of digestive juice were examined and the activity was compared with those of hyoscine-N-butylbromide (HB) and atropine sulfate (Atr). In dogs, TB inhibited the spontaneous and bethanechol-induced motility of various regions of the gastrointestinal tract, the activity being almost the same as that of Atr but stronger than that of HB. All these drugs exhibited a similar inhibitory effect on the motility of the gallbladder. On the contrary, the inhbitory effect of TB on the spontaneous motion of urinary bladder was somewhat weaker than those of HB and Atr, while this effect on the bethanechol-induced motility was nearly equal the effects of HB and Atr. It was also evident that TB inhibited the gastric acid secretion induced by bethanechol: the activity was stronger than that of HB, while it was weaker than that of Atr. Similar effects on the gastric acid secretion were also found in rats. In the case of salivary secretion, however, TB and HB produced much weaker inhibitory actions than Atr. TB even at a higher dose produced little significant effect on the pancreatic and biliary secretion of rats. The uterine contraction induced by methacholine was inhibited by all these drugs. The mydriatic activity of TB in mice was found to be the weakest among the drugs tested.

Topics: Animals; Atropine; Bethanechol Compounds; Bile; Blood Pressure; Butylscopolammonium Bromide; Cats; Depression, Chemical; Dogs; Dose-Response Relationship, Drug; Female; Gallbladder; Gastric Juice; Gastrointestinal Motility; Male; Mice; Muscle Contraction; Muscle, Smooth; Mydriatics; Pancreatic Juice; Piperidines; Rats; Salivation; Thiophenes; Uterine Contraction

The colored substances excreted in bile or urine have bee investigated after adminstration of a high dose of SQ-504 to rats. A reddish-violet colored substance and a bluish-violet colored substance were dominant. Their chemical structures were not assigned because of their small quantity and instability. It was recognized that the colored substances were metabolites of SA-504 from the studies with 3H and 14C labelled SA-504 and the derivatives of SA-504.

Topics: Animals; Bile; Carbon Radioisotopes; Chemical Phenomena; Chemistry; Pigments, Biological; Piperidines; Rats; Structure-Activity Relationship; Thiophenes; Tritium

Topics: Adjuvants, Anesthesia; Adult; Aged; Anesthesia, Epidural; Anesthesia, General; Female; Halothane; Hemodynamics; Humans; Male; Methyl Ethers; Middle Aged; Parasympatholytics; Piperidines; Thiophenes