Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043352 (xerostomia)
 4,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gastric antisecretory effects of two dose levels of pirenzepine given at night were investigated in a group of healthy male volunteers. Compared with placebo, three days of treatment with pirenzepine 100 mg nocte or 150 mg nocte inhibited mean nocturnal intragastric acidity by 54% and 53%, respectively (p less than 0.01). The volume of gastric juice secreted was reduced by 47% and 52% (p less than 0.005), by 100 mg and 150 mg nocte, respectively. Each dose suppressed mean gastric acid output by 67% (p less than 0.001). Pepsin output was not significantly altered. There were no differences in effect between the two dose levels studied, but side-effects such as dry mouth were only seen with the higher dose. Pirenzepine 100 mg is the optimum dose which can conveniently be given at night. This will limit side-effects, and may be a useful treatment for patients with duodenal ulcer.
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PMID:Single nocturnal doses of pirenzepine effectively inhibit overnight gastric secretion. 286 23

Pirenzepine is an antisecretory anticholinergic type drug that has recently been shown to be relatively free of usual anticholinergic side effects on esophageal smooth muscle. It has also been suggested that this drug might release some of the inhibitory control of the esophagus and allow increased muscle contractions. To test this hypothesis, we compared the response of the lower esophageal sphincter (LES) and esophageal peristaltic contractions to bethanechol in 12 healthy controls after background oral doses of placebo, pirenzepine (50 mg), and propantheline (30 mg). After baseline placebo, bethanechol (40 micrograms/kg subcutaneously) produced the expected significant increases in LES pressure and amplitude of peristaltic contractions. Maximal increases were 51.9 +/- 14.9 and 29.5 +/- 7.0%, respectively. Also as expected, propantheline inhibited the cholinergic stimulation from bethanechol, allowing only a 10.1 +/- 13.6% increase in LES pressure and a decrease in peristaltic contraction amplitudes (-44.1 +/- 5.0%) after bethanechol. After background pirenzepine, the responses to bethanechol were intermediate between the other two drugs. A significant increase (44.2 +/- 16.4%) in LES pressure occurred after bethanechol while no significant changes (6.9 +/- 5.8%) were noted in peristaltic amplitudes with this drug. Typical side effects of dry mouth were noted in six of the 12 subjects with propantheline and in only three subjects after pirenzepine. These studies once again confirm the absence of usual anticholinergic side effects with oral pirenzepine compared to oral propantheline in the doses studied. We could find no evidence for a release of cholinergic inhibition after pirenzepine administration.
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PMID:Pirenzepine and propantheline effects on esophageal pressure responses to bethanechol. 287 50

Pirenzepine has been proposed to selectively inhibit gastric acid production. In contrast to classical anticholinergics, pirenzepine does not appear to produce systemic side effects or to strongly inhibit contractions in gastrointestinal tract smooth muscle. This study compares the effects of two doses of pirenzepine (25 and 50 mg per os) with a standard anticholinergic, propantheline, 30 mg per os, and with placebo on esophageal contraction pressures in 12 healthy volunteers in a random double-blind study sequence. No significant change in lower esophageal sphincter pressure (LESP) or in peristaltic pressures occurred with placebo or pirenzepine 25 or 50 mg. However, propantheline produced marked reduction in peristaltic contraction pressures and increased velocity (4 of 12 subjects had complete loss of peristalsis). LESP decrease was almost significant. Seven of 12 subjects experienced dry mouth after propantheline, but none after either dose of pirenzepine or placebo. This study indicates that, as opposed to a classical anticholinergic, pirenzepine does not adversely affect esophageal contraction pressures nor does it have anticholinergic side effects with the oral doses studied.
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PMID:Oral pirenzepine does not affect esophageal pressures in man. 375 24

Pirenzepine is a 'selective' antimuscarinic agent which, unlike classic anticholinergic agents, inhibits gastric acid secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular and urinary functions. On a weight basis, pirenzepine has one-tenth to one-eighth the potency of atropine in inhibiting stimulated gastric acid secretion in humans. Extensive controlled trials utilising endoscopy in outpatients with duodenal ulcers indicate that patient response to pirenzepine is dose related. Doses of 100 to 150 mg/day are superior to placebo in promoting duodenal ulcer healing and in diminishing day and night pain and supplementary antacid consumption. At such doses, the efficacy of pirenzepine appears to be superior to that of gefarnate 300 mg/day and generally not significantly different from that of cimetidine 1 g/day in treating duodenal ulcers. A beneficial effect of pirenzepine in the prevention of duodenal ulcer recurrence was apparent in preliminary studies in small numbers of patients, but its efficacy in this regard needs further confirmation and the optimum dosage determined. Less extensive data on the treatment of benign gastric ulcers suggest that pirenzepine 100 to 150 mg/day is superior to placebo and gefarnate 300 mg/day and does not differ significantly from cimetidine 1 g/day promoting gastric ulcer healing. Pirenzepine is well tolerated by most patients, with a low incidence of typical antimuscarinic effects on the gastrointestinal tract, genitourinary system or heart being reported in clinical studies. However, dry mouth and blurred vision are the more common side effects with clinically effective doses. Thus, pirenzepine appears to have relatively selective antimuscarinic activity, although controlled studies comparing pirenzepine and conventional antimuscarinics in patients with peptic ulcer disease have not been reported.
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PMID:Pirenzepine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in peptic ulcer disease and other allied diseases. 392 24

Pirenzepine is a new anticholinergic agent which selectively binds to gastric mucosal muscarinic receptors. We reviewed the double-blind, therapeutic studies on ulcer patients and the clinical pharmacology for evidence of healing and selectivity. Healing rates of ulcer at doses of 100-150 mg/day varied between 54-84% in trials with 718 duodenal ulcer patients and 630 patients with gastric ulcer. Total side effects incidence in these trials was 18.1%. At 150 mg/day, there was 13.5% incidence of dry mouth, 6.3% incidence of visual disturbance and 2.6% incidence of constipation. In clinical pharmacology trials, pirenzepine moderately inhibited gastric secretion with a slight inhibition of salivary secretion and esophageal motility at 100 mg/day. Higher doses produced the expected parasympatholytic profile, except for the absence of cardioacceleration. We conclude that pirenzepine in low doses, compared to classical antimuscarinic drugs, is relatively selective for gastric hyposecretion. It may be associated with a lower frequency of side effects in therapeutic trials at doses of 100-150 mg/day. Dry mouth and visual disturbance are the most common side effects. Selectivity is dose limited and has so far been demonstrated only at a daily dosage of 100 mg, in 2 divided doses.
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PMID:The efficacy and selectivity of pirenzepine. Review and commentary. 675 18

Effects of pirenzepine on quantitative EEG, heart rate, blood pressure, critical flicker-fusion frequency, vigilance measures, and symptom reports were studied in 23 adult male volunteers under thirty years of age. Oral single doses ranged from 12.5 to 150 mg. Placebo-controlled studies were done in twelve subjects at 100 mg and in ten subjects at 150 mg. Pirenzepine administration was associated with reduced heart rate, dry mouth, and difficulty in focussing near vision. No systematic central activity of the compound was demonstrated at these doses.
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PMID:EEG and behavioral effects of pirenzepine in normal volunteers. 694 76

1. Using rats, we examined the muscarinic receptor subtype mediating pilocarpine-induced parotid salivary secretion and the contributions of ion transporter systems (effluxes of K+ and Cl(-)) and aquaporin-5 (AQP5) translocation to this response in parotid glands in irradiated-induced xerostomia. 2. Salivary secretion was significantly lower in irradiated compared with sham-irradiated (normal) rats. In xerostomia rats, 0.4 and 0.8 mg/kg pilocarpine significantly increased parotid salivary secretion, although the salivary volume was still significantly less than in normal rats after the same dose of pilocarpine. 3. Pirenzepine (1 x 10(-6) to 1 x 10(-1) mol/L), AF-DX 116 (3 x 10(-6) to 3 x 10(-2) mol/L) and N-2-chloroethyl-4-piperidinyl diphenylacetate (4-DAMP; 1 x 10(-8) to 1 x 10(-2) mol/L) dose-dependently displaced radioligand binding to M(1), M(2) and M(3) receptors, respectively, in parotid membranes from both normal and irradiated rats. In each group of rats, 4-DAMP had the highest binding affinity. Pretreatment with 4-DAMP or pirenzepine dose-dependently inhibited pilocarpine-induced parotid secretion in both normal and irradiated rats, with 4-DAMP being markedly more potent than pirenzepine. 4. Normal and irradiated-rat parotid cells did not differ significantly in terms of pilocarpine-induced changes in [Ca2+](i), [K+](i) and [Cl(-)](i). Pilocarpine markedly increased the amount of AQP5 in the apical plasma membrane of parotid cells isolated from normal but not irradiated rats. 5. Thus, pilocarpine induces parotid salivary secretion mainly via the M(3) receptor subtype in both irradiated and normal rats. The reduction in this pilocarpine-induced secretion seen in irradiated rats is due not to disturbances of intracellular Ca2+ mobilization or ion transporter systems, but rather to a disturbance of AQP5 translocation, which may be involved in the pathogenesis of X-ray irradiation-induced xerostomia.
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PMID:Salivation triggered by pilocarpine involves aquaporin-5 in normal rats but not in irradiated rats. 1967 36