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 inhibited cholinesterase (ChE) activities to half the normal level (ID50) was 1.3 x 10(-6) M. This value was higher than those for both physostigmine (PHY; 1.2 x 10(-7) M) and tetrahydroaminoacridine (THA; 3.6 x 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.
Shibanoki
S
S
Department of Pharmacology, Nihon University School of Medicine, Tokyo, Japan.
Ishii
Y
Y
Kubo
T
T
Kogure
M
M
Asai
S
S
Ishikawa
K
K
D000109:Acetylcholine / Q000378:metabolism; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000201:enzymology / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000201:enzymology*; D010830:Physostigmine / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013619:Tacrine / Q000494:pharmacology
D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D011619:Psychotropic Drugs; D013619:Tacrine; D010830:Physostigmine; C049860:amiridine; D002802:Cholinesterases; D000109:Acetylcholine