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.

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.

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.

Nicergoline is a semisynthetic ergoline derivative that has been used as a cerebral vasodilator and in peripheral vascular disease. Nicergoline seems to have an action: (i) as an alpha1-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties. Nicergoline has been suggested to ameliorate cognitive deficits in cerebrovascular disease.

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.

Pyritinol is a semi natural analogue of water soluble vitamin B6. Pyritinol was synthetized way back in 1961 by Merck Laboratories. After years of research, it entered the market in the 1970s, where it was used for clinical applications – including treating stroke patients and those with Alzheimer’s. Since the 1990s, it has been sold as a nootropic dietary supplement in the United States and many other parts of the world. Pyritinol, unlike many other nootropics, has been approved for use as a medical treatment in countries around the world. Doctors in many European countries use Pyritinol to treat patients with chronic degenerative brain disorders – like dementia. Countries where Pyritinol is an approved treatment include Austria, Germany, France, Greece, Italy, and Portugal. France has approved the use of Pyritinol – but only as a treatment for rheumatoid arthritis. Pyritinol is not currently licensed for use in the United Kingdom, but in most other countries, it’s available online or through drug stores as an over the counter substance. Pyritinol is marketed under the brand names Encephabol, Encefabol and Cerbon 6. One of the known mechanisms of action of Pyritinol involves increasing choline uptake into your neurons and thereby increasing acetylcholine levels. Pyritinol is also a great effective precursor to dopamine, which is one of the neurotransmitter mood-boosters in the brain. Pyritinol has better conversion into the neurochemical. This drug increases dopamine, which can keep the brain from anxiety because a lower dopamine level is connected to mood disorders and depression.

Besipirdine is a potential novel first-in-class oral treatment for over active bladder currently in Phase II development, with a mechanism of action clearly different from that of antimuscarinics. It was under evaluation by Aventis up to phase III for Alzheimer’s disease, involving the administration of the compound to over 1500 patients. However, this research has been discontinued. Besipirdine antagonizes alpha-2 and alpha-1 adrenoceptors and inhibits both norepinephrine and serotonin uptake. The most common adverse events were asymptomatic postural hypotension and asymptomatic bradycardia.

Xaliproden is an orally active 5HT1-A receptor antagonist that was being developed by Sanofi. It has been evaluated for the treatment of Alzheimer's disease and amyotrophic lateral sclerosis (ALS), and protection against peripheral neurotoxicity associated with certain cancer chemotherapies. Two large, 18-month, clinical trials of xaliproden (monotherapy or adjunctive therapy, respectively) in patients with mild to moderate AD (MMSE, 16–26, inclusive) were completed in 2007. Failure to demonstrate sufficient efficacy in both trials resulted in cancelation of the xaliproden development program for AD in September 2007.

Meclofenoxate (INN, BAN) (brand name Lucidril), also known as centrophenoxine, is a cholinergic nootropic used as a dietary supplement and drug in the treatment of symptoms of senile dementia and Alzheimer's disease. Meclofenoxate has been shown in studies to be effective in enhancing the memory and in improving the cognitive functions of the elderly. Some studies even suggest that Meclofenoxate has the ability to reverse the signs of brain aging. While claims about its ability as a nootropic agent have not been fully established in clinical trials, some studies do strongly suggest that it is indeed very effective in improving memory retention and recall. Meclofenoxate HCL Powder for Injection is also indicated for the following conditions: comma; skull and brain trauma; following a stroke; encephalopathy; mental disorders (in combination with psychotropic agents); mental and psychomotor retardation in children; brain intoxication; alcohol psychoses; neuritis and polyneuritis. The main mechanism of action of Meclofenoxate is generally believed to be cholinergic in nature. As an efficient transporter of DMAE, Meclofenoxate encourages the production of choline in the brain, which is then synthesized into acetylcholine. The more acetylcholine neurotransmitters in the brain, the better and more efficient the cognitive functions will be. Meclofenoxate also increases cellular membrane phospholipids

Masitinib is a new orally administered tyrosine kinase inhibitor that targets mast cells and macrophages, important cells for immunity, through inhibiting a limited number of kinases. Based on its unique mechanism of action, masitinib can be developed in a large number of conditions in oncology, in inflammatory diseases, and in certain diseases of the central nervous system. In oncology due to its immunotherapy effect, masitinib can have an effect on survival, alone or in combination with chemotherapy. Through its activity on mast cells and consequently the inhibition of the activation of the inflammatory process, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases and the degeneration of these diseases. AB Science is developing masitinib in multiple sclerosis and alzheimer's disease. Masitinib targets kinases, including c-Kit, PDGFR, and Lyn. It is used in the treatment of mast cell tumors in animals, specifically dogs. Since its introduction in November 2008 it has been distributed under the commercial name Masivet. It has been available in Europe since the second part of 2009. In the USA it is distributed under the name Kinavet.