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• W1036843479 abstract "This chapter discusses subsequent literature of those compounds that are still of interest, and more recent compounds, particularly with reference to their mechanism of action. In both rat and human, exogenous 5-HT has little or no ability to affect cholinergic activity. However, the use of 5-hydroxytryptophan, the bio-precursor of 5-HT, causes increased turnover of endogenous 5-HT and a resultant increase in gut cholinergic activity. In cancer patients, high-dose metoclopramide has been shown to reduce emesis evoked by cytotoxic drugs, especially cisplatin. This activity has been linked to its gastric prokinetic activity by some authors, but to its 5-HT receptor antagonism by others. A more potent, conformationally restricted, gut motility stimulant, BRL 24924, has subsequently emerged. Although it is an equatorial isomer, BRL 24924 has no effect on dopamine D2 nor 5-HT1 or 5-HT2 binding sites. BRL 24924 is 10 x more potent than metoclopramide as a stimulant of gastrointestinal motility in rats and is a potent stimulant of electrically-evoked, cholinergically mediated, contractions in guinea-pig isolated ileum. In animal models, cisapride enhances non-adrenergic, non-cholinergic excitatory activity in the gastric antrum of anesthetized ferrets. In the small intestine, it increases antro-duodenal coordination in a dose-dependent manner and an increase in acetylcholine release. In humans, cisapride enhances propulsive colonic peristaltic movements by a non-cholinergic mechanism. It also normalizes the threshold of the inhibitory reflex of the internal anal sphincter, and may, therefore, be of possible therapeutic use in the treatment of constipation. Endogenous peptides undoubtedly play an important role in the control of gastrointestinal function. Studies of the neurochemistry of enteric neurons and of the pharmacology of transmission from these neurons have identified more than 20 potential peptidic neurotransmitters, most of which have demonstrable effects on the gastrointestinal function." @default.
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• W1036843479 date "1988-01-01" @default.
• W1036843479 modified "2023-09-25" @default.
• W1036843479 title "Chapter 21. Gastrointestinal Motility Enhancing Agents" @default.
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• W1036843479 doi "https://doi.org/10.1016/s0065-7743(08)60849-0" @default.
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