The Effects of Cisapride on Antroduodenal Co-ordination and Gastric Emptying

Ag, Johnson

doi:10.3109/00365528909091229

Cited by 29 publications

(13 citation statements)

References 7 publications

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“…However, studies at different concentrations will be needed for complete assessment. One possible cause of the lack of a stimulatory effect of cisapride or metoclopramide is the pig's very rapid gastric emptying (Gregory et al 1990), since in man these prokinetic agents show their strongest effects in individuals with delayed gastric emptying (Behar & Ramsby, 1978;Johnson, 1989). However, these prokinetic agents failed to increase gastric emptying either during the feeding period, or over the 3 h period following the meal, even though the rate of emptying over this latter period is slower than during the feeding period (Gregory et al 1990).…”

Section: Discussionmentioning

confidence: 99%

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Control of gastric emptying in the pig: influence of cholecystokinin, somatostatin and prokinetic agents

Pc¹,

McFadyen²,

Rayner³

1995

Experimental Physiology

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SUMMARYThe influence of systemic arterial infusions of cholecystokinin octapeptide (CCK8) and somatostatin, and injections of cisapride, metoclopramide and atropine on gastric emptying were studied in eight pigs. Gastric emptying of dry matter (DM) and liquids (Cr-EDTA as marker) was measured, in pigs fitted with a gastric cannula, by evacuation of gastnc contents either immediately after the pigs had finished feeding, or 3 h after being fed a meal containing 1200 g of a finely ground barley diet mixed with 2-4 1 water. Gastric emptying of DM and liquids during the feeding period was not significantly altered by cisapride (0.15 and 0-3 mg kg-'-1), metoclopramide (0-2 mg kg-'), CCK8 (250 ng kg-' h-1) or somatostatin (1.8 and 4-5 jug kg-1 h-1); atropine (0.06 mg kg-') slowed emptying of DM (by 53 + 6 %; P < 0 001) and of liquids (by 51 + 7 %, P < 0.01). In contrast, the amount of DM emptied within 3 h of feeding was significantly reduced with CCK8 (250 ng kg-1 h-1; by 14 + 3 %, P < 0.001) and with somatostatin (1 8 jug kg-1 h-1; by 10± 4%; P < 0001). There was no increase in emptying of DM or liquids with cisapride or metoclopramide; indeed, there was actually a reduction in liquid emptying (by 13 + 6%; P < 0 05) with cisapride (0 3 mg kg-'). Gastric emptying in the pig is therefore resistant both to stimulation by prokinetic agents, and to inhibition by some putative neurohormonal modulators at the doses used; gastric emptying during feeding is even more resistant to alteration than is emptying between meals. It is concluded that in the pig, neither CCK nor somatostatin are involved in regulation of gastric emptying during the feeding period, but that both may play a minor role in regulation of emptying between meals. The low sensitivity to CCK may be a factor in the rapid gastric emptying of the pig.

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Section: Discussionmentioning

confidence: 99%

“…it is to some extent inhibited (Johnson, 1989). It needs to be determined if the same also holds true for the pig.…”

Section: Introductionmentioning

confidence: 99%

Control of gastric emptying in the pig: influence of cholecystokinin, somatostatin and prokinetic agents

Pc¹,

McFadyen²,

Rayner³

1995

Experimental Physiology

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“…[85,[149][150][151][152][153] Cisapride stimulates release of acetylcholine from the myenteric plexus, probably via an action on serotonin (5-hydroxytryptamine; 5-HT-4) receptors. [ 150] In addition to their effects on gastric emptying, prokinetic drugs also increase the rate of small intestinal and colonic transit.…”

Section: Prokinetic Agentsmentioning

confidence: 99%

Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

Hebbard

Sun

Bochner

et al. 1995

Clinical Pharmacokinetics

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Although it has been recognised that alterations in gastrointestinal motility, whether induced by physiological or pathological processes, have significant effects on the pharmacokinetics of orally administered drugs, this subject has received inappropriately little attention. Studies relating to this topic have focused on healthy volunteers and animals and have largely been confined to the effects of single drug doses. There is limited information about the effects of disease on pharmacokinetics under steady-state conditions. Changes in gastrointestinal motility may affect the pharmacokinetics of orally administered drugs by altering the rate of delivery, bioavailability or mucosal absorption of the drug. In general the rate of absorption and time taken to achieve maximal plasma concentrations for well absorbed drugs may be modified by changes in gastrointestinal motility, but overall bioavailability is not usually affected. In these cases the therapeutic and clinical effects of the alteration in pharmacokinetics will, therefore, depend on which parameters are important for the action of the drug. For poorly absorbed drugs both the rate of absorption and bioavailability are likely to be altered by changes in gastrointestinal motility. However, the complex effects of food and disease, as well as the properties and formulation of any drug (solubility, ease of dispersion, delayed release formulation) often make the prediction of the magnitude, or even the direction, of any effect difficult to predict. Drugs with direct effects on gastrointestinal motility may influence their own patterns of absorption. In patients with gastrointestinal motility disorders, drugs administered in a controlled release formulation, or those with poor bioavailability, are most likely to have a poorly predictable therapeutic effect. Care should be taken to ensure that the formulation of the drug, its timing of administration in relation to meals and the use of coadministered drugs optimise, or at least ensure consistent absorption.

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“…Further, it was demonstrated that in the antrum and corpus, but not the fundus of the guinea-pig stomach, the electrically evoked out¯ow of tritiated acetylcholine was stimulated after 5-HT 4 receptor stimulation (Takada et al, 1999). In humans, cisapride stimulated antroduodenal motility and gastric emptying (Johnson, 1989;Lux et al, 1994). Additionally, excitatory 5-HT 4 receptors located on cholinergic nerves mediated facilitation of cholinergic neurotransmission in muscle strips of human fundus, corpus and antrum resulting in enhanced contractility (Schuurkes et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

5‐HT₄ receptors mediating enhancement of contractility in canine stomach; an in vitro and in vivo study

Prins

Grijn

Lefebvre

et al. 2001

British J Pharmacology

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We aimed to study 5‐HT4 receptors in canine stomach contractility both in vivo and in vitro. In anaesthetized Beagle dogs, the selective 5‐HT4 receptor agonist prucalopride (i.v.) induced dose‐dependent tonic stomach contractions under isobaric conditions, an effect that was antagonized by the selective 5‐HT4 receptor antagonist GR 125487 (10 μg kg−1, i.v.). Electrical field stimulation (EFS) of corpus longitudinal muscle strips resulted in atropine‐ and tetrodotoxin‐sensitive contractions (L‐NOARG (0.1 mM) present in all organ bath solutions). Prucalopride increased these contractions (maximal response after single‐dose addition (0.3 μM): 165% of initial value, or after cumulative addition: 188%). In the presence of methysergide (3 μM), 5‐HT also increased EFS‐contractions (after single‐dose addition (0.3 μM): increase to 192%, after cumulative addition: 148%). The selective 5‐HT4 receptor antagonists GR 113808 (0.1 μM) or GR 125487 (10 nM) antagonized the prucalopride (0.3 μM)‐induced contraction increments. When EFS‐induced contractions were blocked by atropine or tetrodotoxin, prucalopride was ineffective. In the presence of methysergide (3 μM), the contraction increases to 5‐HT (0.3 μM) were prevented by GR 113808 (0.1 μM). The prucalopride curve (pEC50 7.9) was shifted in parallel to the right by GR 113808 3 nM (pA2 9.4). In the presence of methysergide (3 μM), the curve to 5‐HT (pEC50 8.1) was competitively antagonized by GR 113808, yielding a Schild slope of 0.8±0.2 (pKB of 9.1 with unit Schild slope). In corpus circular muscle strips, the prucalopride (0.3 μM)‐induced augmentation of EFS‐contractions (258%) was also prevented by GR 113808 (0.1 μM) (124%). In conclusion, the effects of 5‐HT4 receptor agonists on proximal stomach motor activity in vivo can be explained by an effect on 5‐HT4 receptors on cholinergic nerves within the gastric muscle wall. British Journal of Pharmacology (2001) 132, 1941–1947; doi:10.1038/sj.bjp.0703985

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The Effects of Cisapride on Antroduodenal Co-ordination and Gastric Emptying

Cited by 29 publications

References 7 publications

Control of gastric emptying in the pig: influence of cholecystokinin, somatostatin and prokinetic agents

Control of gastric emptying in the pig: influence of cholecystokinin, somatostatin and prokinetic agents

Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

5‐HT₄ receptors mediating enhancement of contractility in canine stomach; an in vitro and in vivo study

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The Effects of Cisapride on Antroduodenal Co-ordination and Gastric Emptying

Cited by 29 publications

References 7 publications

Control of gastric emptying in the pig: influence of cholecystokinin, somatostatin and prokinetic agents

Control of gastric emptying in the pig: influence of cholecystokinin, somatostatin and prokinetic agents

Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

5‐HT4 receptors mediating enhancement of contractility in canine stomach; an in vitro and in vivo study

Contact Info

Product

Resources

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5‐HT₄ receptors mediating enhancement of contractility in canine stomach; an in vitro and in vivo study