7-methoxy-tetrahydroaminoacridine (7-MEOTA) is a new reversible cholinesterase inhibitor. Forty-eight young male volunteers divided into six dosage groups were included into a single-dose pharmacokinetic study with either oral (p.o.) or intramuscular (i.m.) administration. The dose of 7-MEOTA was 2, 4 or 8 mg/kg body weight p.o. or 0.5, 1 or 2 mg/kg body weight i.m. in the respective six dosage groups. The plasma levels data were fitted to an open one-compartmental model. The compound showed cholinomimetic adverse effects in 2 subjects with the blood levels exceeding 1,500 micrograms/l. The red blood cells levels paralleled those in plasma and were 2.5 times higher. The tmax was 4 hours and 1 h, t1/2 8.7 +/- 3.9 hours and 6.5 +/- 5.8 hours in case of p.o. and i.m. administration, respectively. The apparent clearance (D/AUC) was 5 times higher following p.o. administration, reflecting the differences in bioavailability.

Prague Psychiatric Center Czechoslovakia

Synthesis and in vitro evaluation of N-(Bromobut-3-en-2-yl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine as a cholinesterase inhibitor with regard to Alzheimer's disease treatment