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

English version

Autoři: Jan Bures ^aff001; Jaroslav Kvetina ^aff001; Vera Radochova ^aff002; Ilja Tacheci ^aff001; Eva Peterova ^aff001; David Herman ^aff003; Rafael Dolezal ^aff004; Marcela Kopacova ^aff001; Stanislav Rejchrt ^aff001; Tomas Douda ^aff001; Vit Sestak ^aff005; Ladislav Douda ^aff001; Jana Zdarova Karasova ^aff003
Působiště autorů: 2nd Department of Internal Medicine—Gastroenterology, Charles University, Faculty of Medicine in Hradec Kralove and University Hospital, Hradec Kralove, Czech Republic ^aff001; Animal Laboratory, University of Defence, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic ^aff002; Department of Toxicology and Military Pharmacy, University of Defence, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic ^aff003; Centre of Biomedical Research, University Hospital, Hradec Kralove, Czech Republic ^aff004; Institute of Clinical Biochemistry and Diagnostics, Charles University, Faculty of Medicine in Hradec Kralove and University Hospital, Hradec Kralove, Czech Republic ^aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227781

Souhrn

Background

Memantine, currently available for the treatment of Alzheimer'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<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<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<0.001), lasting till 120 min. (p<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.

Klíčová slova:

Adverse reactions – Arrhythmia – Blood plasma – Drug absorption – General anesthesia – Kidneys – Receptor physiology – Swine

Zdroje

1. Wang X, Blanchard J, Grundke-Iqbal I, Iqbal K. Memantine Attenuates Alzheimer's Disease-Like Pathology and Cognitive Impairment. PLoS One. 2015; 10(12): e0145441. doi: 10.1371/journal.pone.0145441 26697860

2. Matsunaga S, Kishi T, Iwata N. Memantine monotherapy for Alzheimer's disease: a systematic review and meta-analysis. PLoS One. 2015; 10(4): e0123289. doi: 10.1371/journal.pone.0123289 25860130

3. Chen R, Chan PT, Chu H, Lin YC, Chang PC, Chen CY et al. Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: A meta-analysis. PLoS One. 2017; 12(8): e0183586. doi: 10.1371/journal.pone.0183586 28827830

4. Bures J, Kvetina J, Pavlik M, Kunes M, Kopacova M, Rejchrt S et al. Impact of paraoxon followed by acetylcholinesterase reactivator HI-6 on gastric myoelectric activity in experimental pigs. Neuro Endocrinol Lett. 2013; 34, Suppl 2: 79–83.

5. Bures J, Pejchal J, Kvetina J, Tichy A, Rejchrt S, Kunes M et al. Morphometric analysis of the porcine gastrointestinal tract in a 10-day high-dose indomethacin administration with or without probiotic bacteria Escherichia coli Nissle 1917. Hum Exp Toxicol. 2011; 30: 1955–1962. doi: 10.1177/0960327111403174 21441285

6. Bures J, Smajs D, Kvetina J, Förstl M, Smarda J, Kohoutova D et al. Bacterioinogeny in experimental pigs treated with indomethacin and Escherichia coli Nissle. World J Gastroenterol. 2011; 30: 1955–1962.

7. Kararli TT. Comparison of the gastrointestinal anatomy, physiology and biochemistry of humans and commonly used laboratory animals. Biopharm Drug Dispos. 1995; 16: 351–380. doi: 10.1002/bdd.2510160502 8527686

8. Suenderhauf C, Parrott N. A physiologically based pharmacokinetic model of the minipig: data compilation and model implementation. Pharm Res. 1995; 30: 1–15.

9. Chen JZ, McCallum RW (Eds). Electrogastrography. Principles and Applications. New York: Raven Press, 1994.

10. Parkman HP, Hasler WL, Barnett JL, Eaker EY, American Motility Society Clinical GI Motility Testing Task Force. Electrogastrography: a document prepared by the gastric section of the American Motility Society Clinical GI Motility Testing Task Force. Neurogastroenterol Motil. 2003; 15: 89–102. doi: 10.1046/j.1365-2982.2003.00396.x 12680908

11. Koch KL, Stern RM. Handbook of Electrogastrography. Oxford: Oxford University Press, 2004.

12. Gong Y, Liu Y, Liu F, Wang S, Jin H, Guo F et al. Ghrelin fibers from lateral hypothalamus project to nucleus tractus solitaries and are involved in gastric motility regulation in cisplatin-treated rats. Brain Res. 2017; 1659: 29–40. doi: 10.1016/j.brainres.2017.01.004 28093190

13. Edakkanambeth Varayil J, Ali SM, Tacheci I, Kvetina J, Kopacova M, Kunes M et al. Electrogastrography in experimental pigs. Methodical design and initial experience. Folia Gastroenterol Hepatol. 2009; 7: 98–104. Available from www.pro-folia.org.

14. Tacheci I, Kvetina J, Kunes M, Edakkanambeth Varayil J, Ali SM, Pavlik M et al. Electrogastrography in experimental pigs: the influence of gastrointestinal injury induced by dextran sodium sulphate on porcine gastric erythromycin-stimulated myoelectric activity. Neuroendocrinol Lett. 2011; 32, Suppl 1: 131–136.

15. Tacheci I, Kvetina J, Kunes M, Pavlik M, Kopacova M, Cerny V et al. The effect of general anaesthesia on gastric myoelectric activity in experimental pigs. BMC Gastroenterol. 2013; 13: 48. doi: 10.1186/1471-230X-13-48 23496859

16. Kvetina J, Tacheci I, Pavlik M, Kopacova M, Rejchrt S, Douda T et al. Use of electrogastrography in preclinical studies of cholinergic and anticholinergic agents in experimental pigs. Physiol Res. 2015; 64, Suppl 5: S647–S652.

17. Tveden-Nyborg P, Bergmann TK, Lykkesfeldt J. Basic & Clinical Pharmacology & Toxicology Policy for Experimental and Clinical studies. Basic Clin Pharmacol Toxicol. 2018; 123: 233–235. doi: 10.1111/bcpt.13059 29931751

18. Explanatory Report on the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS 123). Strasbourg: Council of Europe, 2009.

19. Lee TL, Ang SB, Dambisya YM, Adaikan GP, Lau LC. The effect of propofol on human gastric and colonic muscle contractions. Anesth Analg. 1999; 89: 1246–1249. 10553844

20. Schnoor J, Bartz S, Klosterhalfen B, Kuepper W, Rossaint R, Unger JK. A long-term porcine model for measurement of gastrointestinal motility. Lab Anim. 2003; 37: 145–154. doi: 10.1258/00236770360563796 12689426

21. Schnoor J, Unger JK, Kuepper T, Bode B, Hofeditz A, Silny J, Rossaint R. Effects of propofol and fentanyl on duodenal motility activity in pigs. Can Vet J. 2005; 46: 995–1001. 16363326

22. Memiş D, Dökmeci D, Karamanlioğlu B, Turan A, Türe M. A comparison of the effect on gastric emptying of propofol or dexmedetomidine in critically ill patients: preliminary study. Eur J Anaesthesiol. 2006; 23: 700–704. doi: 10.1017/S0265021506000512 16805936

23. Liu MY, Meng S-N, Wu H-Z, Wang S, Wei M-J. Pharmacokinetics of single-dose and multiple-dose memantine in healthy chinese volunteers using an analytic method of liquid chromatography-tandem mass spektrometry. Clin Ther. 2008; 30: 641–653. doi: 10.1016/j.clinthera.2008.04.005 18498913

24. Hiemke C, Bergemann N, Clement HW, Conca A, Deckert J, Domschke K et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry. 2018; 51: 9–62. doi: 10.1055/s-0043-116492 28910830

25. Ametamey SM, Bruehlmeier M, Kneifel S, Kokic M, Honer M, Arigoni M et al. PET studies of 18F-memantine in healthy volunteers. Nucl Med Biol. 2002; 29: 227–231. doi: 10.1016/s0969-8051(01)00293-1 11823128

26. Victorino DB, Bederman IR, Costa ACS. Pharmacokinetic properties of Memantine after a single intraperitoneal administration and multiple oral doses in euploid mice and in the Ts65Dn mouse model of Down's syndrome. Bas Clin Pharmacol Toxicol. 2017; 121: 382–389.

27. Wesemann W, Schollmeyer JD, Sturm G. Distribution of memantine in brain, liver, and blood of the rat. Arzneimittelforschung 1982; 32: 1243–1245. 6891224

28. Karasova JZ, Sestak V, Korabecny J, Mezeiova E, Palicka V, Kuca K et al. 1-Benzyl-4-methylpiperidinyl moiety in donepezil: The priority ticket across the blood-brain-barrier in rats. J Chrom B. 2018; 1092: 350–358.

29. Karasova JZ, Mzik M, Hroch M, Korabecny J, Nepovimova E, Vorisek V et al. The new acetylcholinesterase inhibitors PC-37 and PC-48 (7-methoxytacrine-donepezil-like compounds): Characterization of their metabolites in human liver microsomes, pharmacokinetics and in vivo formation of the major metabolites in rats. Bas Clin Pharmacol Toxicol. 2018; 122: 373–382.

30. Honegger UE, Quack G, Wiesmann UN. Evidence for lysosomotropic of memantine in cultured human cells: cellular kinetics and effects of memantine on phospholipid content and composition, membrane fluidity and beta-adrenergic transmission. Pharmacol Toxicol. 1993; 73: 202–208. doi: 10.1111/j.1600-0773.1993.tb01564.x 8295847

31. Periclou A, Ventura D, Rao N, Abramowitz W. Pharmacokinetic study of memantine in healthy and renally impaired subjects. Clin Pharm Ther. 2006; 79: 134–143.

32. Micuda S, Mundlova L, Anzenbacherova E, Anzenbacher P, Chladek J, Fuksa L, Martinkova J. Inhibitory effects of memantine on human cytochrome P450 activities: prediction of in vivo drug interactions. Eur J Clin Pharmacol. 2004; 60: 583–589. doi: 10.1007/s00228-004-0825-1 15378224

33. Johnson JW, Kotermanski SE. Mechanism of action of memantine. Curr Opin Pharmacol. 2006; 6: 61–67. doi: 10.1016/j.coph.2005.09.007 16368266

34. Johnson J.W.; Glasgow N.G.; Povysheva N.V. Recent insights into the mode of action of memantine and ketamine. Curr Opin Pharmacol. 2015; 20: 54–63. doi: 10.1016/j.coph.2014.11.006 25462293

35. Golovynska I, Beregova TV, Falalyeyeva TM, Stepanova LI, Golovynskyi S, Qu J et al. Peripheral N-methyl-D-aspartate receptor localization and role in gastric acid secretion regulation: immunofluorescence and pharmacological studies. Sci Rep. 2018; 8: 7445. doi: 10.1038/s41598-018-25753-6 29749407

36. Clyburn C, Travagli RA, Browning KN. Acute high-fat diet upregulates glutamatergic signaling in the dorsal motor nucleus of the vagus. Am J Physiol Gastrointest Liver Physiol. 2018; 314: G623–G634. doi: 10.1152/ajpgi.00395.2017 29368945

37. Jocic M, Schuligoi R, Schöninkle E, Pabst MA, Holzer P. Cooperation of NMDA and tachykinin NK(1) and NK(2) receptors in the medullary transmission of vagal afferent input from the acid-threatened rat stomach. Pain. 2001; 89: 147–157. doi: 10.1016/s0304-3959(00)00357-2 11166470

38. Kohjitani A, Funahashi M, Miyawaki T, Hanazaki M, Matsuo R, Shimada M. Peripheral N-methyl-D-aspartate receptors modulate nonadrenergic noncholinergic lower esophageal sphincter relaxation in rabbits. Anesth Analg. 2005; 101: 1681–1688. doi: 10.1213/01.ANE.0000184137.37687.B7 16301241

39. Kuiken SD, Lei A, Tytgat GN, Holman R, Boeckxstaens GE. Effect of the low-affinity, noncompetitive N-methyl-D-aspartate receptor antagonist dextromethorphan on visceral perception in healthy volunteers. Aliment Pharmacol Ther. 2002; 16: 1955–1962. doi: 10.1046/j.1365-2036.2002.01358.x 12390105

40. Seo JH, Fox JG, Peek RM Jr, Hagen SJ. N-methyl D-aspartate channels link ammonia and epithelial cell death mechanisms in Helicobacter pylori infection. Gastroenterology 2011; 141: 2064–2075. doi: 10.1053/j.gastro.2011.08.048 21925124

41. Cremonini F, Delgado-Aros S, Talley NJ. Functional dyspepsia: drugs for new (and old) therapeutic targets. Best Pract Res Clin Gastroenterol. 2004; 18: 717–733. doi: 10.1016/j.bpg.2004.04.003 15324710

42. Landeira-Fernandez J. Participation of NMDA receptors in the lateral hypothalamus in gastric erosion induced by cold-water restraint. Physiol Behav. 2015; 140: 209–214. doi: 10.1016/j.physbeh.2014.12.038 25542887

43. Kohjitani A, Funahashi M, Miyawaki T, Hanazaki M, Matsuo R, Shimada M. Peripheral N-methyl-D-aspartate receptors modulate nonadrenergic noncholinergic lower esophageal sphincter relaxation in rabbits. Anesth Analg. 2005; 101: 1681–1688. doi: 10.1213/01.ANE.0000184137.37687.B7 16301241

44. Jocic M, Schuligoi R, Schöninkle E, Pabst MA, Holzer P. Cooperation of NMDA and tachykinin NK(1) and NK(2) receptors in the medullary transmission of vagal afferent input from the acid-threatened rat stomach. Pain 2001; 89: 147–157. doi: 10.1016/s0304-3959(00)00357-2 11166470

45. Stojiljković MP, Škrbić R, Jokanović M, Bokonjić D, Kilibarda V, Vulović M. Prophylactic potential of memantine against soman poisoning in rats. Toxicology 2019; pii: S0300-483X(19)30061-7. doi: 10.1016/j.tox.2019.01.012 Epub ahead of print. 30682440

46. Almeida AA, Campos DR, Bernasconi G, Calafatti S, Barros FAP, Eberlin MN et al. Determination of memantine in human plasma by liquid chromatography–electrospray tandem mass spectrometry: Application to a bioequivalence study. J Chromatogr B. 2007; 848: 311–316.

47. Bures J, Kvetina J, Tacheci I, Pavlik M, Kunes M, Rejchrt S et al. The effect of different doses of atropine on gastric myoelectrical activity in fasting experimental pigs. J Appl Biomed. 2015; 13: 273–277.

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

Souhrn

Background

Methods

Results

Conclusions

Klíčová slova:

Zdroje

PLOS One

INSIGHTS from European Respiratory Congress

Současné pohledy na riziko v parodontologii

Svět praktické medicíny 3/2024 (znalostní test z časopisu)

Kardiologické projevy hypereozinofilií

Střevní příprava před kolonoskopií