Eseridine (Geneserine) has been known for many years as an anticholinergic agent and used in therapy as a gastrointestinal antispastic. Eseridine salicylate is an inhibitor of cholinesterase activity that has been given by mouth in preparations for dyspepsia and other gastric disorders. It has also been studied for the treatment of Alzheimer’s disease.

Zifrosilone (MDL 73745 or (2,2,2-trifluoro-1-(3-trimethylsilylphenyl)ethanone) is a acetylcholinesterase inhibitor. Zifrosilone was studied as a drug for the treatment of Alzheimer's disease however its development has been discontinued.

Zanapezil (TAK-147) is a selective reversible acetylcholine (ACh) esterase inhibitor that was designed as a drug for Alzheimer's disease (AD) treatment. The development of the drug was discontinued due to a lack of a dose-dependent effect in the trials.

Propoxur (Baygon) is a carbamate insecticide that has recently attracted considerable attention as a possible treatment option for addressing the bedbug epidemic. Propoxur is a non-systemic insecticide with a fast knockdown and long residual effect used against the turf, forestry, and household pests and fleas. The generally accepted mechanism of toxicity for propoxur involves the inhibition of cholinesterase. Propoxur is also used in pest control for other domestic animals, Anopheles mosquitoes, ants, gypsy moths, and other agricultural pests. It can also be used as a molluscicide. Several U.S. states have petitioned the Environmental Protection Agency (EPA) to use propoxur against bedbug infestations, but the EPA has been reluctant to approve indoor use because of its potential toxicity to children after chronic exposure.

Trichlorfon (Metrifonate), the organophosphorous cholinesterase inhibitor, O,O-dimethylhydroxy-2,2,2-trichlorethyl-phosphonate, has been used sporadically in the treatment of human schistosomiasis for a decade. It has selective and variable schistosomicidal activity against S. haematobium that results from its partial metabolism to a highly active anti-cholinesterase, dichlorvos. Schistosomal cholinesterase is more susceptible to this metabolite than that of the human host, but transient reductions in both plasma and erythrocyte cholinesterase activity are demonstrable at therapeutic dosage. However, despite early concerns about its potential toxicity, metrifonate is well tolerated and has been used effectively and extensively in large-scale control programmes. Its potential to enhance central nervous system cholinergic neurotransmission led to clinical trials for the treatment of people with Alzheimer's disease (AD).

Paraoxon is an odorless, reddish-yellow oil. Paraoxon is an aryl dialkyl phosphate where both the alkyl groups are ethyl and the aryl group is 4-nitrophenyl. It is a cholinesterase or acetylcholinesterase (AChE) inhibitor. It is an organophosphate oxon, and the active metabolite of the insecticide parathion. Paraoxon is one of the most potent acetylcholinesterase-inhibiting insecticides available, around 70% as potent as the nerve agent sarin, and so is now rarely used as an insecticide due to the risk of poisoning to humans and other animals. Exposure to Paraoxon can cause rapid, severe organophosphate poisoning with headache, sweating, nausea and vomiting, diarrhea, loss of coordination, and death. Paraoxon is on the Hazardous Substance List because it is cited by DOT and EPA. Parathion is converted in the body in part to paraoxon, a strong inhibitor of the enzyme acetyl cholinesterase. Upon inhibition of this enzyme in the tissues, acetylcholine, the substance responsible for transmission of nerve impulses in much of the nervous system, accumulates, producing an initial overstimulation and subsequent blockage of nerve stimuli. Paraoxon was once used as an opthamological drug against glaucoma.

Velnacrine (9-amino-1,2,3,4-tetrahydroacridin-1-ol) is an inhibitor of acetylcholinesterase. It was studied for the treatment of Alzheimer's disease however development was discontinued. There has been no research into the use of velnacrine as a cognitive enhancer in the treatment of Alzheimer's disease since 1994. The FDA peripheral and CNS drug advisory board voted unanimously against recommending approval. This review shows the toxic nature of velnacrine, and provides no evidence of efficacy.

Acotiamide (Acofide(®)), an oral first-in-class prokinetic drug, is under global development by Zeria Pharmaceutical Co. Ltd and Astellas Pharma Inc. for the treatment of patients with functional dyspepsia. The drug modulates upper gastrointestinal motility to alleviate abdominal symptoms resulting from hypomotility and delayed gastric emptying. It exerts its activity in the stomach via muscarinic receptor inhibition, resulting in enhanced acetylcholine release and inhibition of acetylcholinesterase activity. Acofide® is launched in Japan for treating functional dyspepsia.

Itopride is a dopamine D2 receptor antagonist and inhibitor of acetylcholinesterase. It is indicated in the for the treatment of gastrointestinal symptoms caused by reduced gastrointestinal motility, such as functional non-ulcer dyspepsia (chronic gastritis), gastric fullness, rapid satiation, pain or discomfort in the upper abdomen, anorexia, heartburn, nausea, and vomiting. The drug is not approved in the USA or UK but is available in Japan and Western European countries.

Galantamine (RAZADYNE®, galantamine hydrobromide) is a benzazepine derived from norbelladine. It is found in Galanthus and other Amaryllidaceae. It is a reversible, competitive acetylcholinesterase inhibitor that is used for the treatment of mild to moderate dementia of the Alzheimer’s type. Although the etiology of cognitive impairment in Alzheimer’s disease is not fully understood, it has been reported that acetylcholine-producing neurons degenerate in the brains of patients with Alzheimer’s disease. The degree of this cholinergic loss has been correlated with degree of cognitive impairment and density of amyloid plaques (a neuropathological hallmark of Alzheimer’s disease). While the precise mechanism of galantamine’s (RAZADYNE®, galantamine hydrobromide) action is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. If this mechanism is correct, galantamine’s (RAZADYNE®, galantamine hydrobromide) effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that galantamine (RAZADYNE®, galantamine hydrobromide) alters the course of the underlying dementing process.