The pharmacokinetic parameters and the effect of a single and repeated doses of memantine on gastric myoelectric activity in experimental pigs

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F20%3A10411363" target="_blank" >RIV/00179906:_____/20:10411363 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11150/20:10411363 RIV/60162694:G44__/20:00555842

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=0Oqt4BPe3a" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=0Oqt4BPe3a</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0227781" target="_blank" >10.1371/journal.pone.0227781</a>

Result language

angličtina

Original language name

The pharmacokinetic parameters and the effect of a single and repeated doses of memantine on gastric myoelectric activity in experimental pigs

Original language description

Background: Memantine, currently available for the treatment of Alzheimer&apos;s disease, is an uncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors. Under normal physiologic conditions, these unstimulated receptor ion channels are blocked by magnesium ions, which are displaced after agonist-induced depolarization. In humans, memantine administration is associated with different gastrointestinal dysmotility side effects (vomiting, diarrhoea, constipation, motor-mediated abdominal pain), thus limiting its clinical use. Mechanism of these motility disorders has not been clarified yet. Pigs can be used in various preclinical experiments due to their relatively very similar gastrointestinal functions compared to humans. The aim of this study was to evaluate the impact of a single and repeated doses of memantine on porcine gastric myoelectric activity evaluated by means of electrogastrography (EGG). Methods: Six adult female experimental pigs (Sus scrofa f. domestica, mean weight 41.7+-5.0 kg) entered the study for two times. The first EGG was recorded after a single intragastric dose of memantine (20 mg). In the second part, EGG was accomplished after 7-day intragastric administration (20 mg per day). All EGG recordings were performed under general anaesthesia. Basal (15 minutes) and study recordings (120 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Running spectral analysis based on Fourier transform was used. Results were expressed as dominant frequency of gastric slow waves (DF) and power analysis (areas of amplitudes). Results: Single dose of memantine significantly increased DF, from basic values (1.65+-1.05 cycles per min.) to 2.86 cpm after 30 min. (p = 0.008), lasting till 75 min. (p = 0.014). Basal power (median 452; inter-quartile range 280-1312 μV^2) raised after 15 min. (median 827; IQR 224-2769; p = 0.386; NS), lasting next 30 min. Repetitively administrated memantine caused important gastric arrhythmia. Basal DF after single and repeated administration was not different, however, a DF increase in the second part was more prominent (up to 3.18+-2.16 after 15 and 30 min., p&lt;0.001). In comparison with a single dose, basal power was significantly higher after repetitively administrated memantine (median 3940; IQR 695-15023 μV^2; p&lt;0.001). Next dose of 20 mg memantine in the second part induced a prominent drop of power after 15 min. (median 541; IQR 328-2280 μV^2; p&lt;0.001), lasting till 120 min. (p&lt;0.001). Conclusions: Both single and repeated doses of memantine increased DF. Severe gastric arrhythmia and long-lasting low power after repeated administration might explain possible gastric dysmotility side effects in the chronic use of memantine.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30219 - Gastroenterology and hepatology

Project

<a href="/en/project/GA18-13283S" target="_blank" >GA18-13283S: The influence of experimental gastrointestinal injury and inflammation on pharmacokinetics of Alzheimer's disease drugs</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

PLoS One

ISSN

1932-6203

e-ISSN

—

Volume of the periodical

15

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

e0227781

UT code for WoS article

000534599100060

EID of the result in the Scopus database

2-s2.0-85078260283