Amplification of cortical serotonin release: a further neurochemical action of the vigilance-promoting drug modafinil
Ferraro L, Fuxe K, Tanganelli S,
Fernandez M, Rambert FA, Antonelli T
Department of Experimental and Clinical Medicine,
Section of Pharmacology,
University of Ferrara,
Ferrara, Italy
Neuropharmacology 2000 Oct 1; 39(11):1974-1983


The present in vitro and in vivo studies examined the effects of modafinil on serotonergic transmission in the rat frontal cortex. In the in vitro study modafinil (0.3-30 muM) increased electrically-evoked, but not spontaneous, serotonin ([(3)H]5-HT) efflux from cortical slices in a concentration-dependent manner while the indirect serotonin agonist dl-fenfluramine (1-15 muM) enhanced both spontaneous and evoked [(3)H]5-HT efflux. The effects of modafinil were more pronounced when the 5-HT reuptake was blocked by paroxetine. Contrary to paroxetine (0.3-3 muM) and dl-fenfluramine (1-5 muM), modafinil failed to influence the [(3)H]5-HT uptake. In the in vivo study modafinil (3-100 mg/kg i.p.) increased 5-HT dialysate levels, the maximal effect being already reached at the 30 mg/kg dose. dl-fenfluramine (5 mg/kg) induced an increase in 5-HT levels which was significantly higher than that displayed by modafinil at 30 mg/kg. In the presence of paroxetine (3 muM), the effect of modafinil at 30 mg/kg was higher than that observed in the absence of 5-HT reuptake inhibition. Finally, in the presence of the selective 5-HT(1A) receptor agonist 8-OH-DPAT, modafinil at 100 mg/kg failed to affect 5-HT dialysate levels.These results demonstrate that modafinil regulates cortical serotonergic transmission and suggest that the drug preferentially acts by amplifying the electro-neurosecretory coupling mechanisms and via mechanisms which do not involve the reuptake process.

Modafinil: structure
Modafinil and the aviator
Modafinil: pharmacokinetics
Modafinil and the marmoset
Modafinil versus amphetamine
Modafinil versus methylphenidate
Modafinil v amphetamine v placebo
Serotonin and the genetics of depression
Modafinil plus SSRIs for depression and fatigue
Modafinil (Provigil), serotonin and antidepressants

and further reading

Purchase Modafinil

Future Opioids
BLTC Research
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family