A comparison of a series of newer anticholinergic agents with atropine as regards their effect on saliva flow and gastric secretion in man

Abstract

SYNOPSISThe effect of anticholinergic agents-atropine, propantheline, oxyphencyclimine, and propionyl atropine methyl nitrate-on saliva flow and on hypoglycaemic stimulated gastric secretion has been studied. The acid secretion of the nervous phase of gastric secretion was inhibited by anticholinergic drugs. They influenced gastric secretion to a greater extent than saliva flow.Both propantheline and oxyphencyclimine have a selective action on the stomach superior to atropine. Propionyl atropine methyl nitrate appears to have only weak anticholinergic activity in the dose recommended and is not superior to atropine.Anticholinergic drugs are widely used in the treatment of peptic ulcer and with this aim new preparations are constantly being produced. One of the advantages over atropine claimed for the newer preparations is that they produce fewer side-effects, which implies that they have a selective action on the stomach. Apart from one French study (Lieber, 1956) that showed that the more recently developed preparations were inferior to atropine in this respect, there is no work in man, supported by the quantitative determination of their effect on gastric secretion and of their side-effects, comparing atropine with the newer anticholinergic agents.Because of the importance of whether or not the newer drugs have a selective action on the stomach, the present study was undertaken. Atropine and three new preparations (propantheline, oxyphencyclimine, and propionyl atropine methyl nitrate) were compared as regards their effect on saliva flow and on hypoglycaemic stimulated gastric secretion. METHODFor several reasons it was not possible to determine both responses in the same group of patients. Consequently one group of volunteers was studied as regards saliva flow and a second group as regards gastric secretion; the results were then analysed statistically.Saliva flow was stimulated by chewing. Gum devoid of the outer flavoured coat was used; the gum was chewed for 10 minutes and the volume of saliva secreted measured.Three control readings were taken and subsequently readings at hourly intervals after the administration of the drug until saliva flow returned to normal. Side-effects, particularly the presence of a dry mouth, blurred vision, or difficulty in micturition were noted. The volunteers used in this study were members of the resident medical staff; seven such studies were made.The effect on gastric secretion was determined using hypoglycaemic stimulated secretion. For this, patients having insulin coma therapy for psychiatric reasons were used. After fasting, the drug was given between 6.30 a.m. and 6.45 a.m. followed by a large dose of insulin (the dosage ranged between 200 and 1,600 units). The patient went into coma two to two and a half hours after the administration of insulin and spent one hour in coma. Coma was considered to be present when the patient no longer responded to painful stimuli and extensor plantar responses were present. It had previously been determined that under these conditions c...

Clinical evaluation of three long-acting anticholinergic compounds.

“…Salivary flow measurements have previously beenused to estimate the duration of action and the time of maximal action of various anticholinergic agents, such as atropine (Mushin, Galloon, and Lewis-Faning, 1953), slowly released belladonna alkaloids (Reese, Free, Swintosky, and Grossman, 1959), and synthetic preparations (Grossman, 1958;Piper and Stiel, 1962;Juniper, Stewart, de Vancy, and Smith, 1964). The method described here differs in some respects from those used previously, over which it has several advantages.…”

“…In some of the previous comparative studies (Piper and Stiel, 1962;Juniper et al, 1964) various indices, including gastric secretion, have been measured at arbitrary time intervals after single standard doses of drugs. Since there is considerable individual variation in response, it is uncertain whether the doses of the different drugs used were 8 equivalent, so that such comparisons are of questionable validity.…”

“…The effect of anticholinergic agents on the stomach has been assessed by measuring basal acid secretion (Sun and Shay, 1955;Grossman, 1958;Juniper et al, 1964), secretion in response to a standard meal (Mitchell et al, 1962), to insulin-induced hypoglycaemia (Piper and Stiel, 1962), or to histamine (Seidelin, 1961;Dotevall et al, 1965); but there is no general agreement as to the best method. We have used an infusion of histamine in submaximal dosage, since this is more sensitive than a maximal dose in demonstrating anticholinergic effect (Dotevall, Walan, and Weinfeld, 1967).…”

Clinical Pharmacology and Therapy of Peptic Ulcer Disease

“…Piper and Stiel compared the effect of oral preparations of atropine sulfate 0.7 mg, propantheline 30 mg, oxyphencyclimine 10 mg, and propionyl methyl nitrate 18 mg, on salivary flow and gastric acid secretion. They found that propantheline and oxyphencyclimine had a more selective action on acid secretion inhibition (20). Oxyphencylimine has the advantage over prophantheline of a more prolonged inhibitory action on acid secretion.…”

Medical Management of Peptic Ulcer With reference to anti-ulcer agents in other gastro-intestinal diseases

“…There is as yet , no evidence that anyone preparation has a longer duration than any other if given in doses equipotent at the time of maximal action. Adequate evidence exists that the newer proprietary preparations have a more selective action on the stomach than atropine (Piper and Stiel, 1962 ;Herrmann and Sulway, 1971) and it is hoped that with the further exploitation of this property an effective medical vagotomy will be possible.…”