Design and Study of Piracetam-like Nootropics, Controversial Members of the Problematic Class of Cognition-Enhancing Drugs

Abstract

Cognition enhancers are drugs able to facilitate attentional abilities and acquisition, storage and retrieval of information, and to attenuate the impairment of cognitive functions associated with head traumas, stroke, age and age-related pathologies. Development of cognition enhancers is still a difficult task because of complexity of the brain functions, poor predictivity of animal tests and lengthy and expensive clinical trials. After the early serendipitous discovery of first generation cognition enhancers, current research is based on a variety of working hypotheses, derived from the progress of knowledge in the neurobiopathology of cognitive processes. Among other classes of drugs, piracetam-like cognition enhancers (nootropics) have never reached general acceptance, in spite of their excellent tolerability and safety. In the present review, after a general discussion of the problems connected with the design and development of cognition enhancers, the class is examined in more detail. Reasons for the problems encountered by nootropics, compounds therapeutically available and those in development, their structure activity relationships and mechanisms of action are discussed. Recent developments which hopefully will lead to a revival of the class are reviewed.

Neuroenhancement in Healthy Adults, Part I: Pharmaceutical Cognitive Enhancement: A Systematic Review

“…We classified the presented substances according to their recognized major primary mode of action. Acetylcholine, dopamine, glutamate, histamine and serotonin receptors have been reported to play a fundamental role in cognition [11]. Others like adenosine, cannabinoid, GABA, opioid and sigma receptors seemed to be involved but their role is less clear at the moment.…”

“…Piracetam and piracetam-like molecules are thought to be neuroprotective agents with potential enhancement properties, possibly due to their common 2-oxopyrrolidine structure [11]. Ampakine activity has been established as one of the modes of action of the racetams, however these drugs have multiple modes of action and produce only weak AMPA receptor activation, and it is unclear how significant their ampakine actions are in producing their positive effects.…”

“…An explanation could be that all animal data focused on restoring age-impaired cognitive functions [11].…”

Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings

“…From: John Doe Sent: Wednesday march 21,2012 To: fulvio.gualtieri@unifi.it Subject: DM235 human testing Hello, my name is John Doe I have read many papers on DM235 and other Nootropics. Currently I am a user of Oxiracetam to combat a premature aging syndrome, which causes me severe brain fatigue, loss of memory, etc.…”

4‐Aminopiperidine Derivatives as a New Class of Potent Cognition Enhancing Drugs.

“…Cognition enhancers, 1 often referred to as nootropics, can be defined as drugs able to facilitate attentional abilities and acquisition, storage and retrieval of information, and to attenuate the impairment of cognitive functions associated with age and age-related pathologies. 2 By definition, this class of drugs improves declining of cognitive functions but does not change the rate of progression of neurodegeneration.…”