A better nootropic (or drug that is more nootropic) has higher benefit to side-effect ratio.
Emoxypine. Emoxypine was first synthesized by L.D. Smirnov and K.M. Dumayev, then studied and developed in the Institute of Pharmacology, Russian Academy of Medical Sciences and National Scientific Center of Bioactive Substances Safety. In Russia, emoxypine has a wide range of applications in medical practice. It purportedly exercises anxiolytic, anti-stress, anti-alcohol, anticonvulsant, nootropic, neuroprotective and anti-inflammatory action.  Emoxypine presumably improves cerebral blood circulation, inhibits thrombocyte aggregation, lowers cholesterol levels, has cardioprotective and antiatherosclerotic action.[medical citation needed] Emoxypine is deemed useful as an anxiolytic medication with few side effects (i.e. no sedation, impairment, tolerance or addition potential) compared to benzodiazepines. [medical citation needed] One study determined the effectiveness of emoxypine in 205 patients with clinical manifestations of lumbosacral radiculopathy (LSR).
Jump up ^ W. Meclofenoxate. Meclofenoxate (Lucidril), also known as centrophenoxine, is a drug used to treat the symptoms of senile dementia and Alzheimer's disease. It is an ester of dimethylethanolamine (DMAE) and 4-chlorophenoxyacetic acid (pCPA). DMAE is a natural substance, found especially in fish. pCPA is a synthetic compound that resembles a variety of plant hormones called auxins. In elderly patients, it has been clinically shown to improve memory, have a mentally stimulating effect, and improve general cognition. Meclofenoxate also increases cellular membrane phospholipids.  It is also used off-label as a nootropic, often combined with a racetam drug such as piracetam.  Side effects and contraindications Meclofenoxate is generally considered safe. See also References BAY 73-6691. BAY 73-6691 is a drug developed by Bayer for the treatment of Alzheimer's disease. It was the first compound developed that acts as a phosphodiesterase inhibitor selective for the PDE9A subtype.
The PDE9A enzyme is expressed primarily in the brain, with high concentrations in the cerebellum, neocortex, striatum, and hippocampus, and acts to limit the cGMP-mediated signal transduction which occurs following glutamate binding to NMDA receptors. Consequently selective PDE9A inhibitors were predicted to prolong intracellular responses to glutamate and enhance glutamate signalling, and since this process is known to be involved in learning and memory, PDE9A inhibitors should have a nootropic effect and may be useful in the treatment of Alzheimer's. Jump up ^ Wunder F, Tersteegen A, Rebmann A, Erb C, Fahrig T, Hendrix M. Characterization of the first potent and selective PDE9 inhibitor using a cGMP reporter cell line. Molecular Pharmacology. 2005 Dec;68(6):1775-81.
Ensaculin. Ensaculin (KA-672) is a drug from the coumarin family, which has been researched as a potential treatment for dementia. It acts on a number of receptor systems, being both a weak NMDA antagonist and a 5HT1A agonist. Animal studies have shown promising nootropic effects, although efficacy in humans has yet to be proven. It was well tolerated in human trials, with the main side effect being orthostatic hypotension (low blood pressure). Jump up ^ Lishko, PV; Maximyuk, OP; Chatterjee, SS; Nöldner, M; Krishtal, OA (1998). "The putative cognitive enhancer KA-672.HCl is an uncompetitive voltage-dependent NMDA receptor antagonist". Galantamine. Galantamine (Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine) is used for the treatment of mild to moderate Alzheimer's disease and various other memory impairments, in particular those of vascular origin.
It is an alkaloid that is obtained synthetically or from the bulbs and flowers of Galanthus caucasicus (Caucasian snowdrop, Voronov's snowdrop), Galanthus woronowii (Amaryllidaceae) and related genera like Narcissus (daffodil)), Leucojum (snowflake), and Lycoris including Lycoris radiata (Red Spider Lily). Studies of usage in modern medicine began in the Soviet Union in the 1950s. The active ingredient was extracted, identified, and studied, in particular in relation to its acetylcholinesterase (AChE)-inhibiting properties. The bulk of the work was carried out by Soviet pharmacologists M. D. The first industrial process was developed in Bulgaria by prof. It is available in both a prescription form and as an over the counter supplement.
Pharmacology Pharmacokinetics Bifemelane. Bifemelane (Alnert, Celeport) is a pharmaceutical drug used in the treatment of senile dementia in Japan. It has nootropic, neuroprotective, and antidepressant effects, and acts through the cholinergic system in the brain. Bifemelane is also useful for the treatment of glaucoma. See also References Jump up ^ David J. Triggle (1996). S-17092. S-17092 is a drug which acts as a selective inhibitor of the enzyme Prolyl endopeptidase. This enzyme is involved in the metabolic breakdown of a number of neuropeptide neurotransmitters in the brain, and so inhibiting the action of the enzyme increases the activity of these neuropeptides.
This produces nootropic effects which make S-17092 a promising and novel treatment for neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease. See also References Jump up ^ Barelli H, Petit A, Hirsch E, Wilk S, De Nanteuil G, Morain P, Checler F. S 17092-1, a highly potent, specific and cell permeant inhibitor of human proline endopeptidase. Linopirdine. Linopirdine is a putative cognition-enhancing drug with a novel mechanism of action. Linopirdine blocks the KCNQ2\3 heteromer M current with an IC50 of 2.4nM disinhibiting acetylcholine release, and increasing hippocampal CA3-schaffer collateral mediated glutamate release onto CA1 pyramidal neurons. In a murine model linopirdine is able to nearly completely reverse the senescence-related decline in cortical c-FOS, an effect which is blocked by atropine and MK-801, suggesting Linopirdine can compensate for the age related decline in acetylcholine release. Linopirdine also blocks homomeric KCNQ1 and KCNQ4 voltage gated potassium channels which contribute to vascular tone with substantially less selectivity than KCNQ2/3. See also References ^ Jump up to: a b Schnee, M.
Calea ternifolia. It is used in traditional medicine and ritual in its native range. Uses In Mexico the plant is used as an herbal remedy for dysentery and fever. The Zoque Popoluca people call the plant tam huñi ("bitter gum") and use it to treat diarrhea and asthma, and the Mixe people know it as poop taam ujts ("white bitter herb") and use it for stomachache and fever. The Chontal people of Oaxaca reportedly use the plant, known locally as thle-pela-kano, during divination. Isolated reports describe rituals that involve smoking a plant believed to be this species, drinking it as a tea, and placing it under a pillow to induce divinatory dreams. Chemical composition Cultivated specimen Chemical compounds isolated from this species include flavones such as acacetin and sesquiterpene lactones such as germacranolides. The sesquiterpenes known as caleicines and caleochromenes may be active in its effects on sleep. Law The plant is not a controlled substance in Australia.
Fipexide. Fipexide (Attentil, Vigilor) is a psychoactive drug of the piperazine chemical class which was developed in Italy in 1983. It was used as a nootropic drug in Italy and France, mainly for the treatment of senile dementia, but is no longer in common use due to the occurrence of rare adverse drug reactions including fever and hepatitis.
Fipexide is similar in action to other nootropic drugs such as piracetam and is structurally similar to another more well-known nootropic, centrophenoxine. Chemically, it is an amide union of parachlorophenoxyacetate and methylenedioxybenzylpiperazine, and notably, has been shown to metabolize to the latter, which plays a significant role in its effects. See also References Jump up ^ Missale C, Pasinetti G, Govoni S, Spano PF, Trabucchi M. Idebenone. Idebenone (pronounced eye-deb-eh-known, trade names Catena, Raxone, Sovrima, among others) is a drug that was initially developed by Takeda Pharmaceutical Company for the treatment of Alzheimer's disease and other cognitive defects. This has been met with limited success. The Swiss company Santhera Pharmaceuticals has started to investigate it for the treatment of neuromuscular diseases.
In 2010, early clinical trials for the treatment of Friedreich's ataxia and Duchenne muscular dystrophy have been completed. As of December 2013[update] the drug is not approved for these indications in North America or Europe. Chemically, idebenone is an organic compound of the quinone family. It is also promoted commercially as a synthetic analog of coenzyme Q10 (CoQ10). Uses Indications that are or were approved in some territories Nootropic effects and Alzheimer's disease Friedreich's ataxia (Sovrima) Indications being explored Other neuromuscular diseases