CNS Drug Reviews, Vol. 4, No. 3, Fall 1998

Ipidacrine (NIK-247, 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline monohydrochloride monohydrate) is a novel substance synthesized by the National Research Center for Biologically Active Compounds in the Russian Federation. Ipidacrine was earlier referred to by the chemical name amiridine (7). This compound contains the structure of 4-aminopyridine and is structurally very similar to tacrine (9-amino-l,2,3,4-tetrahydroacridine hydrochloride hydrate), as is shown in Fig. 1. It has been reported that ipidacrine blocks specific [3H]tacrine binding (43). Tacrine is an antidementia agent that can inhibit acetylcholinesterase (EC 3.1.1.1.7, AChE) (21,26,48,50). Senile dementia has been associated with a loss of cholinergic neurotransmission, which is essential for some cognitive functions (20,53). Degeneration of basal forebrain cholinergic neurons in the nucleus basalis of Meynert (NBM) and deficiencies of acetylcholine and choline acetyltransferase (EC 2.3.1.6.) are known to occur in Alzheimer’s disease (10,72). This cholinergic hypothesis has led to the development of compounds that are capable of improving cholinergic neurotransmission in the brain. Among the various approaches to enhancement of the cholinergic system, inhibition of the degrading enzyme (AChE) is presently the most promising in terms of providing candidate drugs for treatment of patients with dementia (16,32,57,63). Recently, tacrine and E-2020 (1-benzyl-4-[{5,6-dimethoxy1-indanon}-2-yl]methylpiperidine hydrochloride, Eisai Co., Ltd., Tokyo, Japan), a pure AChE inhibitor, won FDA approval for treating Alzheimer’s Disease (Fig. 1) (57). A number of additional AChE inhibitors await approval; however, CI-1002 is not one of them, since it was disqualified in phase I clinical trials. Therefore, we discuss in this paper