Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs.
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.
Gualtieri
Fulvio
F
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via G. Capponi 9, I-50121, Firenze, Italy. fulvio.gualtieri@unifi.it
Manetti
Dina
D
Romanelli
Maria Novella
MN
Ghelardini
Carla
C
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy; D015195:Drug Design; D006801:Humans; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D010889:Piracetam / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013678:Technology, Pharmaceutical / Q000379:methods*
D018697:Nootropic Agents; D000109:Acetylcholine; D010889:Piracetam