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Modafinil and Central Alpha 1-adrenergic Stimulation

There’s no getting around the fact that the abstract below is densely packed with extremely specific scientific terminology.  It summarizes research into whether stimulating certain areas of the brain impacts the behaviors stimulated by the drug Modafinil.  As expected the study found that Modafinil has a significant cognitive and wakefulness effect on both rodents and primates.  The study also suggests that this effect may be due to the “modulation (stimulation) of central alpha 1-adrenoceptors” in the brain.  Interestingly, however, the study unexpectedly found that there were no effects on the functions of the peripheral nervous system associated with the alpha 1-adrenoceptrors (for example no salivation or pilomuscle contractions)


What this means for the bigger picture

The finding that Modafinil improves cognition and wakefulness in both rodents and primates goes a long way to confirming the role of Modafinil as an effective stimulant. 

The unexpected results of the study also indicate how little is truly known about the mechanisms through which psychostimulants like Modafinil act.  The study therefore points towards the usefulness of research into their mechanisms of action and interaction wihin the wakefulness promoting agents sub family of medicine. 



The study draws interesting conclusions, however it is limited in that it is entirely animal based.  For Modafinil to be proven as an effective stimulant further research and testing of its interactions in humans is necessary.

Moreover, the study was conducted back in 1990, meaning that more than a quarter of a century has passed since its results were published.  Numerous other theories in regards to mechanisms of action have since been published.


So what does this mean for Modafinil?

This study was one of the first of its kind in that it looked for and identified a possible mechanism through which Modafinil acted.  In many ways it gave a starting point from which a much broader base of knowledge could be formed.

The study adds to the suggestion that Modafinil is an effective stimulant, potentially with less peripheral nervous system side effects than expected.


Further Reading

For another theory on Modafinil’s mechanism of action this study discusses orexin/hypocretin and forebrain sites of action.

There’s also this study on rhesus monkeys looking at how Modafinil may be able to offset the effects of sleep deprivation on cognitive function.


See below for the complete abstract with key findings in bold.


Central alpha 1-adrenergic stimulation in relation to the behaviour stimulating effect of modafinil; studies with experimental animals
Duteil J, Rambert FA, Pessonnier J,
Hermant JF, Gombert R, Assous E
Centre de Recherches du Laboratoire L. Lafon,
Maisons-Alfort, France.
Eur J Pharmacol 1990 May 3; 180(1):49-58


Single administration of the new drug modafinil was followed by an increase in locomotor activity in mice and in nocturnal activity in monkeys. Stereotyped behaviour in mice and rats, and potentiation of amphetamine-induced stereotyped behaviour were not observed; however, at the highest dose used, a slight potentiation of apomorphine-induced stereotyped behaviour was observed in rats. The modafinil-induced increase in locomotor activity in mice was prevented by the centrally acting alpha 1-adrenoceptor antagonists, prazosin and phenoxybenzamine, and by reserpine but not by the mixed dopamine D-1/D-2 antagonist, haloperidol, the dopamine D-2 antagonist, sulpiride, the peripherally acting alpha 1-adrenoceptor antagonist, phentolamine, the alpha 2-adrenoceptor antagonist, yohimbine, the beta-adrenoceptor antagonist, propranolol, or by the catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine. Likewise, the modafinil-induced increase in nocturnal activity in monkeys was prevented by prazosin. Interestingly, modafinil did not produce obvious peripheral sympathetic effects in mice and rats (no salivation, no contraction of the pilomotor muscles, slight mydriasis only at high doses). Therefore, modafinil appears to produce a strong stimulating effect in rodents and in primates. These effects could be linked to modulation (stimulation) of central alpha 1-adrenoceptors unaccompanied by peripheral sympathetic effects, which is unexpected.