The effect of single and repeated doses of rivastigmine on gastric myoelectric activity in experimental pigs.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
09
04
2022
accepted:
16
05
2023
medline:
5
6
2023
pubmed:
1
6
2023
entrez:
1
6
2023
Statut:
epublish
Résumé
Rivastigmine is a pseudo-irreversible cholinesterase inhibitor used for therapy of Alzheimer's disease and non-Alzheimer dementia syndromes. In humans, rivastigmine can cause significant gastrointestinal side effects that can limit its clinical use. The aim of this study was to assess the impact of rivastigmine on gastric motor function by means of electrogastrography (EGG) in experimental pigs. Six experimental adult female pigs (Sus scrofa f. domestica, hybrids of Czech White and Landrace breeds; 3-month-old; mean weight 30.7 ± 1.2 kg) were enrolled into the study twice and created two experimental groups. In group A, a single intragastric dose of 6 mg rivastigmine hydrogen tartate was administered in the morning to fasting pigs before EGG recording. In group B, rivastigmine was administered to overnight fasting animals in a dietary bolus in the morning for 7 days (6 mg per day). On day 8, an intragastric dose of 12 mg rivastigmine was given in the morning to fasting pigs before EGG. EGG recording was accomplished by means of an EGG standalone system. Recordings from both groups were evaluated in dominant frequency and EGG power (areas of amplitudes). In total, 1,980 one-minute EGG intervals were evaluated. In group A, basal EGG power (median 1290.5; interquartile range 736.5-2330 μV2) was significantly higher in comparison with the power of intervals T6 (882; 577-1375; p = 0.001) and T10 (992.5; 385-2859; p = 0.032). In group B, the dominant frequency increased significantly from basal values (1.97 ± 1.57 cycles per minute) to intervals T9 (3.26 ± 2.16; p < 0.001) and T10 (2.14 ± 1.16; p = 0.012), respectively. In group B, basal EGG power (median 1030.5; interquartile range 549-5093) was significantly higher in comparison with the power of intervals T7 (692.5; 434-1476; p = 0.002) and T8 (799; 435-1463 μV2; p = 0.004). Both single as well as repeated intragastric administration of rivastigmine hydrogen tartrate caused a significant decrease of EGG power (areas of amplitudes) in experimental pigs. EGG power may serve as an indirect indicator of gastric motor competence. These findings might provide a possible explanation of rivastigmine-associated dyspepsia in humans.
Sections du résumé
BACKGROUND
Rivastigmine is a pseudo-irreversible cholinesterase inhibitor used for therapy of Alzheimer's disease and non-Alzheimer dementia syndromes. In humans, rivastigmine can cause significant gastrointestinal side effects that can limit its clinical use. The aim of this study was to assess the impact of rivastigmine on gastric motor function by means of electrogastrography (EGG) in experimental pigs.
METHODS
Six experimental adult female pigs (Sus scrofa f. domestica, hybrids of Czech White and Landrace breeds; 3-month-old; mean weight 30.7 ± 1.2 kg) were enrolled into the study twice and created two experimental groups. In group A, a single intragastric dose of 6 mg rivastigmine hydrogen tartate was administered in the morning to fasting pigs before EGG recording. In group B, rivastigmine was administered to overnight fasting animals in a dietary bolus in the morning for 7 days (6 mg per day). On day 8, an intragastric dose of 12 mg rivastigmine was given in the morning to fasting pigs before EGG. EGG recording was accomplished by means of an EGG standalone system. Recordings from both groups were evaluated in dominant frequency and EGG power (areas of amplitudes).
RESULTS
In total, 1,980 one-minute EGG intervals were evaluated. In group A, basal EGG power (median 1290.5; interquartile range 736.5-2330 μV2) was significantly higher in comparison with the power of intervals T6 (882; 577-1375; p = 0.001) and T10 (992.5; 385-2859; p = 0.032). In group B, the dominant frequency increased significantly from basal values (1.97 ± 1.57 cycles per minute) to intervals T9 (3.26 ± 2.16; p < 0.001) and T10 (2.14 ± 1.16; p = 0.012), respectively. In group B, basal EGG power (median 1030.5; interquartile range 549-5093) was significantly higher in comparison with the power of intervals T7 (692.5; 434-1476; p = 0.002) and T8 (799; 435-1463 μV2; p = 0.004).
CONCLUSIONS
Both single as well as repeated intragastric administration of rivastigmine hydrogen tartrate caused a significant decrease of EGG power (areas of amplitudes) in experimental pigs. EGG power may serve as an indirect indicator of gastric motor competence. These findings might provide a possible explanation of rivastigmine-associated dyspepsia in humans.
Identifiants
pubmed: 37262057
doi: 10.1371/journal.pone.0286386
pii: PONE-D-22-10515
pmc: PMC10234519
doi:
Substances chimiques
Rivastigmine
PKI06M3IW0
Cholinesterase Inhibitors
0
Phenylcarbamates
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0286386Informations de copyright
Copyright: © 2023 Tsianou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Neurogastroenterol Motil. 2023 Feb;35(2):e14418
pubmed: 35699340
Expert Opin Drug Saf. 2014 Jun;13(6):759-74
pubmed: 24845946
Clin Ther. 1998 Jul-Aug;20(4):634-47
pubmed: 9737824
Biopharm Drug Dispos. 1995 Jul;16(5):351-80
pubmed: 8527686
Life Sci. 2021 Jul 15;277:119492
pubmed: 33864819
Scand J Gastroenterol. 2019 Jan;54(1):8-17
pubmed: 30638082
Biomed Eng Online. 2022 Jun 27;21(1):43
pubmed: 35761323
PLoS One. 2020 Jan 24;15(1):e0227781
pubmed: 31978146
Pharmaceuticals (Basel). 2021 Jun 18;14(6):
pubmed: 34207410
Neurogastroenterol Motil. 2017 May;29(5):
pubmed: 28035728
Hepatogastroenterology. 2008 Jul-Aug;55(85):1492-6
pubmed: 18795720
Physiol Res. 2015;64(Suppl 5):S647-52
pubmed: 26674291
Life Sci. 2018 Jul 15;205:1-8
pubmed: 29746845
Acta Medica (Hradec Kralove). 2015;58(4):131-4
pubmed: 26960826
Neuro Endocrinol Lett. 2015;36 Suppl 1:150-5
pubmed: 26757120
J Cent Nerv Syst Dis. 2021 Jul 7;13:11795735211029113
pubmed: 34285627
Molecules. 2021 Apr 09;26(8):
pubmed: 33918638
IEEE Rev Biomed Eng. 2019;12:287-302
pubmed: 30176605
J Alzheimers Dis. 2022;85(3):1195-1204
pubmed: 34924395
Transl Res. 2015 Jul;166(1):12-27
pubmed: 25655839
Pharm Res. 1998 Oct;15(10):1614-20
pubmed: 9794506
Dig Dis Sci. 1998 Jan;43(1):80-9
pubmed: 9508540
Dig Dis Sci. 2000 Mar;45(3):525-8
pubmed: 10749328
Curr Pharm Des. 2017;23(12):1873-1876
pubmed: 27908270
Clin Interv Aging. 2017 Apr 18;12:697-707
pubmed: 28458525
Pharmaceuticals (Basel). 2021 Nov 09;14(11):
pubmed: 34832918
Cureus. 2022 Jan 16;14(1):e21295
pubmed: 35186557
Neurogastroenterol Motil. 2003 Apr;15(2):89-102
pubmed: 12680908
Am J Physiol Gastrointest Liver Physiol. 2022 Oct 1;323(4):G295-G305
pubmed: 35916432
J Clin Pharmacol. 2001 Oct;41(10):1082-90
pubmed: 11583476
World J Gastroenterol. 2020 May 21;26(19):2333-2348
pubmed: 32476797
Neuropharmacology. 2021 Jun 1;190:108352
pubmed: 33035532
J Pharmacol Toxicol Methods. 2016 Nov - Dec;82:37-44
pubmed: 27475721
Clin Pharmacokinet. 2002;41(3):225-34
pubmed: 11929322
J Clin Gastroenterol. 2009 Sep;43(8):716-22
pubmed: 19247205
PLoS One. 2021 Sep 13;16(9):e0257311
pubmed: 34516588
Cochrane Database Syst Rev. 2015 Sep 22;9:CD001191
pubmed: 26393402