Effect of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta-(b)-quinoline monohydrate hydrochloride (NIK-247) on cholinergic enzyme activity in rats

An in vitro comparison demonstrated that the concentration of NIK-247 that the inhibited cholinesterase (ChE) activities to half the normal level (ID 50) was 1.3 × 10 −6 M. This value was higher than those for both physostigmine (PHY; 1.2 × 10 −7 M) and tetrahydroaminoacridine (THA; 3.6 × 10 −7 M), which are used as cholinesterase inhibitors in the treatment of cholinergic deficits. Neither NIK-247 nor THA affected the activity of choline acetyltransferase (ChAT). These inhibitions of ChE by NIK-247 and PHY lasted for 2 h, while that by THA lasted for over 4 h. In the effects of NIK-247 and PHY, the concentrations of intrastriatal acetylcholine (ACh) were changed in relation to the inhibition of the ChE activity. However, THA caused a transient increase in the ACh level lasting for only 2 h instead of inhibiting the enzyme activity for over 4 h. These findings suggest that NIK-247 is a drug with a similar profile in its effect on cholinergic neurons to PHY, the prototype drug among ChE inhibitors. The data indicate that NIK-247 may be useful as a drug for the treatment of central as well as peripheral deficits of the cholinergic mechanism.