Dextran Sodium Sulphate-Induced Gastrointestinal Injury Further Aggravates the Impact of Galantamine on the Gastric Myoelectric Activity in Experimental Pigs

Abstract

Galantamine has been used as a treatment for Alzheimer disease. It has a unique, dual mode of action (inhibitor of acetylcholinesterase and allosteric modulator of nicotinic acetylcholine receptors). Nausea (in about 20%), vomiting (10%) and diarrhoea (5–7%) are the most common side effects. The aim of this study was to assess the effect of galantamine on porcine gastric myoelectric activity without (Group A) and with (Group B) dextran sodium sulphate (DSS)-induced gastrointestinal injury. Galantamine hydrobromide was administrated to twelve pigs as a single intragastric dose (24 mg). Gastric myoelectric activity was investigated by electrogastrography (EGG). Basal (15 min before galantamine administration) and study recordings after galantamine administration (300 min) were evaluated using a running spectral analysis. Results were expressed as dominant frequency of gastric slow waves and power analysis (areas of amplitudes). Altogether, 3780 one-minute EGG recordings were evaluated. In Group A, power was steady from basal values for 180 min., then gradually decreased till 270 min. (p = 0.007). In Group B, there was a rapid gradual fall from basal values to those after 120 min. (p = 0.007) till 300 min. (p ˂ 0.001). In conclusion, galantamine alone revealed an unfavourable effect on porcine myoelectric activity assessed by gastric power. It can be a plausible explanation of galantamine-associated dyspepsia in humans. DSS caused further profound decrease of EGG power. That may indicate that underlying inflammatory, ischaemic or NSAIDs-induced condition of the intestine in humans can have aggravated the effect of galantamine on gastric myoelectric activity.

The effect of single and repeated doses of rivastigmine on gastric myoelectric activity in experimental pigs

“…In our experimental setting, we have found that similar decrease in EGG power was also revealed in pigs after the administration of other acetylcholinesterase inhibitors, i.e., donepezil [ 10 ] and galantamine [ 11 ]. The difference was more evident in animals with a longer intestinal transit time compared to those with a shorter intestinal transit time [ 11 ]. Notably, we used a single low dose of ketamine (an NMDA blocker) as induction to anaesthesia, so a possible gastric myoelectric effect of ketamine might have influenced the basal EGG recording.…”

“…Thorough analysis of nearly two thousand one-minute EGG intervals has provided a detailed information of the impact of rivastigmine on porcine gastric motor activity. Based on previous studies of other acetylcholinesterase inhibitors [10,11], similar effects of rivastigmine in humans and pigs could be expected.…”

“…To the best of our knowledge, there has been no literature concerning rivastigmine in experimental pigs published so far. However, based on studies with donepezil and galantamine [ 10 , 11 ], we expect a similar effect of rivastigmine, i.e., class effect of acetylcholinesterase inhibitors, on gastric motor function in experimental pigs. Furthermore, similar findings in humans can be anticipated as the physiology of the gastrointestinal tract of pigs is similar to that of humans [ 12 – 14 ].…”

“…Limited explanation is provided by the cholinergic effect of rivastigmine. In our previous work, we evaluated the effect of memantine [ 9 ] as well as the effect of acetylcholinesterase inhibitors (donepezil, galantamine) [ 10 , 11 ] on gastric myoelectric activity in experimental pigs. To the best of our knowledge, there has been no literature concerning rivastigmine in experimental pigs published so far.…”

Wireless Monitoring of Gastrointestinal Transit Time, Intra-luminal pH, Pressure and Temperature in Experimental Pigs: A Pilot Study

“…There are only sparse experimental studies available so far (32,(39)(40)(41). The most detailed data on the use of Similar variability features were found in experimental porcine electrogastrography, too (35)(36)(37)(38). In this study, we decided to deliver the wireless capsule endoscopically, so that gastric content could be removed from the stomach before the capsule was placed (drunk water, gastric juice, wireless motility capsules in experimental pigs was published by Henze et al (32).…”