Basically, Provigil stimulates different brain chemicals in different parts of the brain than amphetamines do. As a result, Provigil does not cause the anxiety, jitteriness or euphoria that result from using amphetamines. It doesn’t appear to cause dependence either. In other words, the same dose of Provigil continues to work the same, but you need an ever larger dose of amphetamines to get the same result. Both drugs increase dopamine levels, but if you give someone a dopamine agonist Provigil still does its job but amphetamines don’t.
Provigil seems to actually turn the brain’s “I don’t need to sleep” switch on, as opposed to amphetamines which seem to turn the “I will not sleep even though I need to” switch on.
Provigil is in an entirely new class of pharmaceutical – the Eugeroics (“good arousal”). Amphetamines are in the pharmaceutical class called the Amphetamines, or sometimes the Substituted Amphetamines.
They have different chemical structures. Provigil’s formula is C 15 H 15 NO 2 S while a typical amphetamine formula is C 9 H 13 N.
Some background information:
According to Wikipedia, “Modafinil [aka Provigil or 2—[di(phenyl)methylsulfinyl]acetamide), like other stimulants, increases the release of monoamines but also elevates hypothalamic histamine levels, leading some researchers to consider Modafinil a “wakefulness promoting agent” rather than a classic amphetamine-like stimulant.” ( http://en.wikipedia.org/wiki/Modafinil )
To me this means that amphetamines increase the release of monoamines, but Provigil both increases the release of monoamines and histamine levels in the hypothalamus.
The specific monoamines increased by Provigil are dopamine in the striatum and nucleus accumbens, noradrenaline in the hypothalamus and ventrolateral preoptic nucleus, and serotonin in the amygdala and frontal cortex. Modafinil is thought to have less potential for abuse than other stimulants due to the absence of any significant euphoric or pleasurable effects.
Amphetamines (aka 1-phenylpropan-2-amine) apparently increase the levels of norepinephrine, serotonin, and dopamine (in the nigrostriatal region of the brain), inducing euphoria and with a strongly addictive potential.
And according to http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19505:
“Administration of either amphetamine or methylphenidate evoked Fos-like immunoreactivity in a large number of neurons in the striatum and whole cortex, especially in the caudate nucleus and mediofrontal cortex, which are known to be dopaminergic targets. In contrast, administration of modafinil resulted in the labeling of few cells in these structures, but did induce marked Fos labeling in neurons of the anterior hypothalamic nucleus and adjacent areas.”
http://modafinil-adrafinil.com/ summarizes a lot of the differences between Provigil and Amphetamines.
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