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.

Lappaconitine is an alkaloid isolated from the root of Aconltitum sinomantanum Nakai. It has a strong analgesic activity that does not involve the opioid receptor. It was shown to have class-I antiarrhythmic action and irreversibly blocks cloned human heart (hH1) channels by binding to the site 2 receptor.

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.

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.

Meptazinol is a unique opioid analgesic. Binding studies suggest a relative selectivity for mu-1 opioid receptor sites. Meptid is indicated for the treatment of moderate to severe pain, including post-operative pain, obstetric pain and the pain of renal colic. The most commonly reported adverse reactions after treatment with meptazinol are nausea, vomiting, dizziness, diarrhoea and increased sweating, constipation, abdominal pain, rash, vertigo, headache, drowsiness, somnolence and dyspepsia.

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.

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.

Ipidacrine (Neiromidin) is a drug first synthesized by the National Research Center for Biologically Active Compounds in the Russian Federation. Neuromidin has a direct stimulating effect on the conduct of the pulse along the nerve fibers, interneuronal and neuromuscular synapses of the CNS and peripheral nervous system. Pharmacological action neuromidin is based on a combination of two mechanisms of action: blockade of potassium channels of the membrane of neurons and muscle cells; reversible inhibition of cholinesterase in synapses. Neuromidin enhances the effect on smooth muscle acetylcholine not only, but epinephrine, serotonin, histamine and oxytocin. It has the following pharmacological effects: - Improve and stimulate impulse conduction in the nervous system and neuromuscular transmission; - Enhances contractility of smooth muscle organs under the influence of acetylcholine agonists, adrenaline, serotonin, histamine and oxytocin receptors, with the exception of potassium chloride; - Improves memory, slows progressive course of dementia. In preclinical studies Neuromidin is not teratogenic, embryotoxic, mutagenic, carcinogenic and immunotoxic action, had no effect on the endocrine system

Ipidacrine (Neiromidin) is a drug first synthesized by the National Research Center for Biologically Active Compounds in the Russian Federation. Neuromidin has a direct stimulating effect on the conduct of the pulse along the nerve fibers, interneuronal and neuromuscular synapses of the CNS and peripheral nervous system. Pharmacological action neuromidin is based on a combination of two mechanisms of action: blockade of potassium channels of the membrane of neurons and muscle cells; reversible inhibition of cholinesterase in synapses. Neuromidin enhances the effect on smooth muscle acetylcholine not only, but epinephrine, serotonin, histamine and oxytocin. It has the following pharmacological effects: - Improve and stimulate impulse conduction in the nervous system and neuromuscular transmission; - Enhances contractility of smooth muscle organs under the influence of acetylcholine agonists, adrenaline, serotonin, histamine and oxytocin receptors, with the exception of potassium chloride; - Improves memory, slows progressive course of dementia. In preclinical studies Neuromidin is not teratogenic, embryotoxic, mutagenic, carcinogenic and immunotoxic action, had no effect on the endocrine system

Lappaconitine is an alkaloid isolated from the root of Aconltitum sinomantanum Nakai. It has a strong analgesic activity that does not involve the opioid receptor. It was shown to have class-I antiarrhythmic action and irreversibly blocks cloned human heart (hH1) channels by binding to the site 2 receptor.