Cognitive Enhancers (Nootropics). Part 3: Drugs Interacting with Targets other than Receptors or Enzymes. Disease-modifying Drugs

Abstract

Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 19 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease modifying drugs, meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-β and tau. For drugs, whose mechanism of action is not known, they are either classified according to structure, e.g., peptides, or their origin, e.g., natural products. The review covers the evolution of research in this field over the last 25 years.

Neurotransmitters and Memory

“…Notably, aging, AD, and amnesia are associated to decrements in 5-HT markers such as SERT and in the number of 5-HT 1A-1B, 5-HT 2A/2C , 5-HT 4 , 5-HT 6 , and 5-HT 7 receptors (for references see Rodríguez et al, 2012;Xu et al, 2012). Also emerging evidence indicates that memory formation, amnesia, promnesic and amnesic drugs modify serotonergic markers, including 5-HT receptors, SERT, and serotonergic tone (Belcher et al, 2005;Callaghan et al, 2012;Da Silva Costa-Aze et al, 2012;Eriksson et al, 2012;Fournet et al, 2012;Frankland et al, 2013;Froestl et al, 2012Froestl et al, , 2013Garcia-Alloza et al, 2004;Goldenhuys and Van der Schyf, 2009;Gong et al, 2012;Haahr et al, 2012;Hermann et al, 2012;Huerta-Rivas et al, 2010;Jones and Moller, 2011;Lorke et al, 2006;Liy-Salmeron, 2008;Marin et al, 2012a;Marin et al, 2012b;Marcos et al, 2006Marcos et al, , 2008Marshall and O'Dell, 2012;Mathur and Lovinger, 2012;Meneses et al, , 2011aNa et al, 2012;Pérez-García et al, 2006;Pérez-García and Meneses, 2008a;Pérez-García and Meneses, 2009;Tellez et al, 2010Tellez et al, , 2012. Certainly, in this context, 5-HT systems, protocols of training/testing, memory tasks and drugs (see e.g., Meneses, 2013) deserve attention.…”

Substituted piperazines as nootropic agents: 2- or 3-phenyl derivatives structurally related to the cognition-enhancer DM235

“…1 Several cellular mechanisms have been found to modulate cognition, offering different strategies to overcome cognitive dysfunction. Recently, Froestl et al have reviewed cognitive enhancers according to their molecular targets, [2][3][4] including in their survey also compounds whose mechanism of action has not been fully elucidated, such as piracetam, 1 and 2. 2 We have previously described the cognition-enhancing activity of 1 and 2 (respectively, DM232, Unifiram, and DM235, Sunifiram, Chart 1) which potently reversed scopolamine-induced amnesia in different behavioral tests in rodents.…”

Cassia tora A Potential Cognition Enhancer in Rats with Experimentally Induced Amnesia

“…Cognitive function involves memory, attention, perception, language and psychomotor functions. 1 Nootropics are drugs commonly used to treat cognitive defect in AD patient.…”