Impact of tacrine and 7-methoxytacrine on gastric myoelectrical activity assessed using electrogastrography in experimental pigs.

ABSTRACT

OBJECTIVES: Tacrine was the first acetylcholinesterase inhibitor approved for therapy of Alzheimer's disease. It has currently been withdrawn in some countries mostly due to the risk of hepatotoxicity and might be replaced by its derivate 7-methoxytacrine (7-MEOTA). The aim of this study was to assess the impact of these two compounds on gastric myoelectrical activity by means of surface cutaneous electrogastrography (EGG). METHODS: Twelve pigs (Sus scrofa f. domestica, weighing 30-35 kg) entered the study. A single dose of tacrine (200 mg i.m., n=6) or 7-MEOTA (200 mg i.m., n=6) was administrated. All EGG recordings were performed under general anaesthesia in the morning after 24 hours of fasting. Basal (30 minutes) and study recordings (150 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Results were expressed as dominant frequency of gastric slow waves, power analysis (areas of amplitudes) and power ratio assessment (ratio of the areas of amplitudes after and before study drug administration). RESULTS: Tacrine decreased EGG dominant frequency 10 minutes after its administration (from basal 3.1±0.6 to 2.8±0.6 cycles per minute; p=0.014). Tacrine induced a non-significant 60-minute increase of the power (with maximal value 493±533 µV2 at 20 minutes) and power ratio (with maximal value 2.04±3.4 at 10 minutes). Tacrine caused substantial gastric arrhythmia. 7-MEOTA did not influence dominant frequency of gastric slow waves significantly. 7-MEOTA caused a short-term late increase of the power ratio at 60 minutes (6.3±11.2; p=0.003). Blood cholinesterase activity did not correlate with any EGG parameter either after tacrine or 7-MEOTA at any time. CONCLUSIONS: Tacrine and 7-MEOTA have different impacts on EGG. Tacrine decreased dominant frequency and induced long-lasting gastric arrhythmia. 7-MEOTA caused a short-term late increase of the EGG power in experimental pigs.