As mentioned, piracetam (Nootropil®) was the first active ingredient in the class of nootropic drugs. Chemically, piracetam can be defined as a cyclic derivative of GABA (the inhibitory neurotransmitter also known as gamma-aminobutyric acid).
Currently, piracetam is indicated for the treatment of cortical myoclonus, but it can also be used to treat mild cognitive impairment in elderly patients and to stimulate brain activity in Alzheimer’s patients.
Piracetam carries out its action by interacting with the AMPA receptor, a particular type of ionotropic receptor involved in the conduction of excitatory stimuli and in learning and memorization processes. The endogenous substrates of AMPA, in fact, are precisely excitatory neurotransmitters such as glutamate.
Piracetam is able to activate this receptor (despite the chemical structure similar to that of GABA), producing a cascade of chemical signals that leads to an improvement in cognitive functions.
Aniracetam (Ampamet®) is another nootropic drug used in the treatment of elderly patients with attention and memory disorders of degenerative origin (as occurs, for example, in the case of Alzheimer’s disease) or of vascular origin.
It is an analog of the aforementioned piracetam, but appears to be much more potent than the latter.
The mechanism of action by which aniracetam carries out its action is comparable to that of piracetam. In fact, even aniracetam positively modulates the AMPA receptor, favoring and stimulating cognitive functions.
However, the scientific world is still divided on what concerns the real effectiveness of these drugs. Precisely due to the fact that cognitive functions are regulated by a set of different and complex mechanisms, some scholars believe the usefulness of this type of active ingredients is doubtful.
Methylphenidate (Ritalin®) is an active ingredient with a psychostimulating and nootropic action, which is used in the treatment of attention deficit hyperactivity disorder (ADHD).
In fact, methylphenidate has been shown to increase the brain activity of ADHD patients, improving their attention and concentration. At the same time, however, methylphenidate is also able to exert a sort of calming action, reducing the impulsive behaviors that typically occur in patients suffering from this disease.
The exact mechanism of action by which methylphenidate exerts these activities has not yet been fully elucidated. However, some scholars believe that this active ingredient exerts its action by inhibiting the reuptake of dopamine and, to a lesser extent, noradrenaline, resulting in an increase in dopaminergic and noradrenergic signals.
Modafinil (Provigil®) is another drug belonging to the category of psychostimulants and nootropics. However, this active ingredient is not normally used to increase and improve cognitive functions, but it is indicated for the treatment of narcolepsy.
Thanks to its psychostimulating action, in fact, modafinil helps patients suffering from this pathology to maintain a state of wakefulness.
In some cases, however, modafinil has also been used as an off-label drug in the treatment of ADHD and the results obtained appear to be very encouraging, as an improvement in the cognitive abilities of treated patients has been highlighted. The mechanism of action, with which modafinil allows the maintenance of the wakeful state and with which it exerts its nootropic action, is not yet fully understood.
From some studies, however, it seems to have emerged that modafinil – similarly to the aforementioned methylphenidate – is able to inhibit the reuptake of dopamine and noradrenaline through the binding with the transporters of these neurotransmitters. All this therefore translates into an increase in dopaminergic and noradrenergic transmissions.
Furthermore, modafinil is also able to weakly interact with numerous other receptors involved in the body’s sleep / wake mechanisms (such as, for example, GABA, histamine or melatonin receptors). In any case, the dopamine and noradrenaline reuptake inhibition theory seems to be the most plausible one in explaining the nootropic effects induced by this active ingredient.