In a rapidly evolving society, with an always increasing exposure to saturating information and requirements in terms of mental performance, there is a growing demand of drugs able to sustain mental functions such as memory, cognition, intelligence, motivation, attention and concentration even for healthy people. Such drugs, named nootropics, smart drugs, memory enhancers, cognitive enhancers and intelligence enhancers consists in drugs, supplements, nutraceuticals, and functional food [1]. Main features of nootropics are the enhancement of learning and memory acquisitions as well as resistance of learned behaviors to agents that tend to impair them as well as protection of brain against various physical or chemical injuries and finally facilitation of interhemispheric flow of information and efficient tonic cortical/subcortical mechanism [2]. Absence of the usual negative pharmacologic effects of psychotropic drugs is also expected, since these agents are dedicated among others to healthy, both young and aging, patients. These drugs that improve performance on cognitive tasks in healthy individuals are typically developed to treat cognitive incapacities and improve the quality of life for patients suffering of neuropsychiatric disorders and brain injury [3].
Facing social pressure, more and more people are prompted to use drugs usually prescribed for treating disabling diseases in the sole aim of raising their working and efficiency potential, without regarding at the potential side effects or addiction provoked by a misuse of such drugs. The growing market demand for such drugs or supplements makes that several drugs or dietary supplements are available to the consumer, over the counter, without any positive effect on memory or related mental functions that has been formally scientifically demonstrated.
Precise mechanisms of action of nootropics are unknown. Extensive studies have revealed various pharmacological effects. It is supposed that they act by altering the availability of the brain's supply of neurochemicals such as neurotransmitters, enzymes, and hormones by improving the brain's oxygen supply, or by stimulating nerve growth.
Nootropics belong to many different categories, that are the following: traditional herbs, vitamins and supplements, recreational drugs, racetams, stimulants, dopaminergics, concentration and memory enhancement (cholinergics, GABA blockers, glutamate activators, phosphodiesterase inhibitors, Alpha-2A adrenergic receptor agonists), serotonergics, anti-depression, adaptogenic (antistress) and mood stabilization agents, vasodilators improving blood flow and metabolic function, histamine agonists (experimental), antioxidant and neuroprotectant drugs, hormones and secondary enhancers.
Piracetam that belongs to the racetam category was the first nootropic agent discovered and licensed in many countries for myoclonus, stroke and mild cognitive impairment. Piracetam is among the toxicologically safest drugs ever developed. As an example, it has been reported that a two week regimen of piracetam enhanced verbal memory in healthy college students [4]. It also displayed therapeutic benefit in schizophrenic patients when combined with typical neuroleptics [5]. Other drugs showed improvement in cognitive functions, such as d-cycloserine in anxiety disorders [6], levetiracetam in epilepsy [7,8] and alcohol withdrawal [9], and donepezil in mental retardation [10] amongst others. But most of these drugs are not devoid from detrimental side effects.
Baclofen, a GABAB receptor agonist, is known to induce anterograde amnesia in rodents [11]. More recently, recurrent spells of amnesia have been reported in a woman subjected to intrathecal instillation of baclofen in the frame of a treatment for dystonia [12]. Similarly, a clinical study about the effects of acamprosate on healthy young human subjects has shown that acamprosate impairs free recall, supporting the hypothesis that acamprosate impairs memory functions [13].
As shown herein, the inventors have found combinations of particular drugs that are efficient to stimulate cognition in vivo, particularly in healthy subjects, and which represent novel improved safe and efficient nootropic agents.