Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: Neuronally mediated muscle contractions and relaxations of human colon were evoked by electrical field stimulation (EFS) and defined phenotypically as cholinergic, nitrergic or tachykinergic using pharmacological tools; the effects of drugs were determined as changes in 'area under the curve'. KEY RESULTS:
Prucalopride increased cholinergically mediated contractions (EC50 855 nM; 33% maximum increase), consistent with its ability to stimulate intestinal motility; donepezil (477%) and neostigmine (2326%) had greater efficacy. Concentrations of donepezil (30-100 nM) found in venous plasma after therapeutic doses had minimal ability to enhance cholinergic activity. However, donepezil (30 nM) together with prucalopride (3, 10 μM) markedly increased EFS-evoked contractions compared with prucalopride alone (P = 0.04). For example, the increases observed with donepezil and prucalopride 10 μM together or alone were, respectively, 105 ± 35%, 4 ± 6% and 35 ± 21% (n = 3-7, each concentration). CONCLUSIONS AND IMPLICATIONS:
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Authors | J Broad, V W S Kung, G Boundouki, Q Aziz, J H De Maeyer, C H Knowles, G J Sanger |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 170
Issue 6
Pg. 1253-61
(Nov 2013)
ISSN: 1476-5381 [Electronic] England |
PMID | 24032987
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2013 The British Pharmacological Society. |
Chemical References |
- Benzofurans
- Cholinesterase Inhibitors
- Indans
- Piperidines
- Serotonin 5-HT4 Receptor Agonists
- prucalopride
- Donepezil
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Benzofurans
(pharmacology)
- Cholinesterase Inhibitors
(pharmacology)
- Colon
(drug effects, physiology)
- Donepezil
- Drug Synergism
- Female
- Gastrointestinal Motility
(drug effects)
- Humans
- In Vitro Techniques
- Indans
(pharmacology)
- Male
- Middle Aged
- Muscle Contraction
(drug effects)
- Piperidines
(pharmacology)
- Serotonin 5-HT4 Receptor Agonists
(pharmacology)
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