7-methoxytacrine (MEOTA) is a reversible inhibitor of acetylcholinesterase and it belongs to a group of drugs, which are known as activators of cognitive functions and could be useful in the therapy of some neurodegenerative disorders such as Alzheimer’s disease. The lower toxicity is its advantage in comparison with tacrine. L-carnitine (CRT) was used to increase penetration of MEOTA through the blood brain barrier in rat. ³H-MEOTA was administered intravenously (5 mg/kg), orally (5 and 0.5 mg/kg) or intramuscularly (100 mg/kg) to rats in order to evaluate its pharmacokinetic properties. The intramuscular administration was chosen for the biodistribution study, where MEOTA was administered in two groups of rats: one group was administered only with MEOTA and the second group was administered CRT (300 mg/kg) orally for 3 consecutive days before MEOTA. Levels of MEOTA Were assessed in blood and in the brain tissue samples. In the next experimental step it was evaluated inhibition of acetylcholinesterase (AChE) activity in separate brain areas following administration of MEOTA in interaction with CRT. The results showed that MEOTA crossed blood brain barrier and its levels in the brain were weakly increased after CRT repeated administration. On the other hand the repeated administration of CRT enhanced significantly the inhibiting effect of 7-MEOTA on the brain AChE activity. A comparison of the brain tissue levels of MEOTA under the influence of CRT with the inhibiting eflect on the AChE activity in the brain showed that the higher inhibiting effect of MEOTA on AChE activity with CRT is not caused by a global increasing of its concentration in the brain tissue, but it is probably due to an interaction of MEOTA and CRT on active centre of the corresponding enzyme.

Keywords: Toxicology; 7-methoxytacrine; acetylcholinesterase