Clinical evaluation of three long-acting anticholinergic compounds.

Kaye, Michael; Rhodes, J.; Sweetnam, P. M.

doi:10.1136/gut.9.5.590

Cited by 8 publications

(5 citation statements)

References 11 publications

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“…Osyphencyclimine is a powerful anticholinergic with prolonged action on saliva flow as well as gastric secretion (PI- PER, ELLIOTT, SIETSMA & PRYOR 1960). With three doses during the day a constant inhibitory effect can be obtained and even night secretion is controlled (PIPER & STIEL 1962). The present study confirmed the marked difference in the individual response to an anticholinergic drug (SUN & SHAY 1956, PIPER & STIEL 1962, KAYE, RHODES & SWEETNAM 1968).…”

Section: Discussionsupporting

confidence: 86%

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Experimental palatal candidosis and saliva flow in monkeys

Olsen

Haanæs

1977

European J Oral Sciences

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– Maxillary acrylic plates, inoculated with Candida albicans, were inserted for 3 weeks in 10 monkeys (Cercopithecus aethiops) (Series I), and reinserted in five of the animals 8 weeks after removal (Series II). To suppress saliva flow oxyphencyclimine was injected intramuscularly (0.125 mg/kg) thrice daily for 3 weeks in six monkeys of Series I, while four controls received no drug. In Series II the oxyphencyclimine dose was doubled in three animals, and two controls were sham‐treated with sodium chloride. Mean saliva flow was reduced to 58 % after 1 week and to 63 % after 3 weeks with the low dose of oxyphencyclimine. The values with the high dose were 56 % and 64 %, respectively. After 1 week thrush had developed beneath the plates of all monkeys. The patches were more extensive and regressed slower with oxyphencyclimine. Enlarged lesions were seen with the double dose, In Series I intraepithelial invasion by hyphae was detected more frequently and longer after inoculation in the oxyphencyclimine group. Such invasion was not found in biopsies from Series II. It is likely that saliva offers some protection against yeasts colonizing the fitting side of a denture.

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Section: Discussionsupporting

confidence: 86%

“…This naay be related to a more sustained saliva depression with the high dose. When two different doses of another long-acting anticholinergic, glycopyrronium, were tested in man, both yielded the same maximum inhibition of saliva flow (40 %), but the action of the higher dose lasted longer (KAYE et al 1968).…”

Section: Discussionmentioning

confidence: 98%

Experimental palatal candidosis and saliva flow in monkeys

Olsen

Haanæs

1977

European J Oral Sciences

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“…Such a design was not chosen because of the report (Hunt and Wales, 1966) that prolonged continuous administration of poldine to patients with peptic ulcer reduced acid secretion for considerable periods after drug withdrawal. In fact, there was no evidence in our patients that basal or maximal acid output were reduced beyond the period of drug administration though both drugs used in this trial have been shown to inhibit gastric acid secretion as provoked by a variety of stimuli (Moeller, 1962;Posey, 1962;Sun, 1962;Abbott, Sourial, Krieger, and Levey, 1962;Barman and Larson, 1963;Dotevall, Schroder, and Walan, 1965;Christianson and Rodbro, 1967;Kaye, Rhodes, and Sweetnam, 1968). Indeed, basal output, measured seven days after treatment was stopped, was increased in patients who had received anticholinergic drugs, significantly so in those given glycopyrronium.…”

Section: Discussionmentioning

confidence: 66%

A controlled trial of glycopyrronium and l-hyoscyamine in the long-term treatment of duodenal ulcer

Kaye¹,

Rhodes²,

Beck³

et al. 1970

Gut

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SUMMARY A controlled single-blind trial has been carried out to determine the value of long-term anticholinergic therapy in duodenal ulcer. Of 106 male patients with symptomatic and radiologically proven duodenal ulcer admitted to the trial, 91 completed the study. Patients were divided randomly into three groups. They received either glycopyrronium, or 1-hyoscyamine in a sustained-release form, or inert tablets for one year.Progress was judged on the basis of frequency and severity of symptoms, monthly assessments by patients, antacid consumption, and radiology. By all criteria, glycopyrronium and 1-hyoscyamine were not significantly superior to placebo. Symptomatic improvement, both subjective and objective, occurred in approximately 80% of all patients during the year of observation; there was no significant difference between the groups.Because anticholinergic agents reduce gastric motility and acid secretion, they have been used extensively in the treatment of peptic ulcer. In Britain the annual expenditure on such drugs is about two million pounds. Their value, however, in clinical practice is disputed and conclusions from clinical trials, many of which were uncontrolled, are conflicting.We have attempted in this study to assess the value of two anticholinergic drugs-one a natural alkaloid, the other a synthetic compound-in the long-term treatment of patients with duodenal ulceration.Method PATIENTS One hundred and six male patients (aged between 20 and 65) were admitted to the trial. They had had symptoms of peptic ulcer during the previous six months, and had had an ulcerated and/or deformed,duodenal cap demonstrated by radiology.At the first interview, the nature and purpose of the trial were explained, and a standard ques-

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“…It is felt, however, that it is valid to consider the structure-activity relationship from the standpoint of the system having combined antiulcer-antisecretory activity especially as consideration of either one of the tests would lead to the same overall structure-activity relationships. Replacement of sulfur by oxygen, e.g., 3 and 4, results in a loss of activity, a feature which has been noted before10 and which is not perhaps too surprising considering the different chemical nature of amides and thioamides.…”

mentioning

confidence: 53%

“…The main disadvantage of antacid therapy is that these agents have a very short duration of action2 and it is well known that anticholinergic drugs have limited therapeutic value in depressing gastric secretion in peptic ulcer patients, because the doses effective in the inhibition of acid secretion cause unpleasant side actions associated with blockade of parasympathetic stimulation. 3 In recent years, a number of nonanticholinergic antisecretory agents have been reported. Among the most notable of these are pyridyl-2-thioacetamide (CMN 131), 4 2-methoxy-lV-methyl-2-(2-pyridyl)thioacetamide (SKF 59377),5 2-phenyl-2-(2-pyridyl)thioacetamide (SC 15 396), 4 and the histamine H2-receptor antagonists burimamide,4 metiamide,4 and cimetidine.6…”

mentioning

confidence: 99%

5,6,7,8-Tetrahydroquinolines. 4. Antiulcer and antisecretory activity of 5,6,7,8-tetrahydroquinolinenitriles and -thioamides

Beattie¹,

Crossley²,

Curran³

et al. 1977

J. Med. Chem.

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A number of 5,6,7,8-tetrahydroquinoling-8-nitriles and -8-thioamides and related compounds have been found to be potent inhibitors of basal gastric secretion in the pylorus-ligated rat and to afford protection against gastric erosions induced in rats by cold-restraint stress. Molecular manipulation has proved useful in determining factors necessary for such activity and structure-activity relationships are discussed. It has been shown that the most necessary requirements for activity are a pyridine nitrogen with its available lone pair and a primary or secondary thioamide. Also desirable is a six-membered carbocyclic ring with relative freedom from steric hinderance around the 8 position.

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Clinical evaluation of three long-acting anticholinergic compounds.

Cited by 8 publications

References 11 publications

Experimental palatal candidosis and saliva flow in monkeys

Experimental palatal candidosis and saliva flow in monkeys

A controlled trial of glycopyrronium and l-hyoscyamine in the long-term treatment of duodenal ulcer

5,6,7,8-Tetrahydroquinolines. 4. Antiulcer and antisecretory activity of 5,6,7,8-tetrahydroquinolinenitriles and -thioamides

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