source:
https://forums.psychcentral.com/psychiatric-medications/254913-1-amphetamines-modafinil-armodafinil-their-effectiveness-effects-brainModafinil is a unique wakefulness-promoting pharmaceutical whose exact biochemical mechanism of action
is not known. However, it has been shown to increase the levels of serotonin, histamine, and dopamine in the
brain.. Studies done on the wakefulness-promoting mechanism of modafinil have proposed specific activation
of the tuberomammillary, a cluster of magnocellular cells in the posterior hypothalamus. Which is the main source of neuronal histamine in the brain.
Also it produces activation on orexin (a neurotransmitter that regulates arousal, wakefulness, and appetite containing neurons in the perifornical area, although not in other areas involved in the sleep–wake cycle (eg, the supraoptic nucleus).
Histamine and
OrexinWiki have been implicated in the regulation of wakefulness.
source:
http://www.scielo.brModafinil administration into rat nucleus accumbens resulted in a weak dopamine release secondary to its ability to reduce local γ-aminobutyric acidergic transmission.
By contrast, amphetamine strongly elevated dopamine levels in the nucleus accumbens and striatum. The difference in addiction potential between modafinil and amphetamine is postulated and explained by this difference in dopaminergic activity.
Modafinil is also known to decrease GABA release from the hypothalamus.
Modafinil appears to be distinct from other psychostimulants (eg, amphetamine) by being highly selective for specific areas in the central nervous system (nuclei of the hypothalamus and amygdala) rather than widespread brain activation and has little effect on dopaminergic activity in the striatum.
Technical Abstract In clinical drug development, wakefulness and wake-promotion maybe assessed by a large number of scales and questionnaires. Objective assessment of wakefulness is most commonly made using sleep latency/maintenance of wakefulness tests, polysomnography and/or behavioral measures.
The purpose of the present review is to highlight the degree of overlap in the assessment of wakefulness and cognition, with consideration of assessment techniques and the underlying neurobiology of both concepts.
DesignReviews of four key areas were conducted: commonly used techniques in the assessment of wakefulness; neurobiology of sleep/wake and cognition; targets of wake promoting and/or cognition enhancing drugs; and ongoing clinical trials investigating wake promoting effects.
ResultsThere is clear overlap between the assessment of wakefulness and cognition. There are common techniques which may be used to assess both concepts; aspects of the neurobiology of both concepts may be closely related; and wake promoting drugs may have nootropic properties (and vice-versa). Clinical trials of wake promoting drugs often, though not routinely, assess aspects of cognition.
ConclusionsRoutine and broad assessment of cognition in the development of wake promoting drugs may reveal important nootropic effects, which are not secondary to alertness/wakefulness, whilst existing cognitive enhancers may have under explored or unknown wake promoting properties.