Potentiation of brain serotonin activity may inhibit seizures, especially in drug-resistant epilepsy

Med Hypotheses. 2008;70(4):876-9. doi: 10.1016/j.mehy.2007.06.039. Epub 2007 Sep 7.


In spite of the large number of antiepileptic drugs (AEDs) actually available, the problem of drug-resistant epilepsy has not been solved. No AEDs are efficacious in patients with pharmacoresitant epilepsy, so new hypothesises about the mechanisms of pharmacoresistance are needed. In the last years the ideas on the role of brain serotonin in epilepsy have been turned upside down: increasing the available brain serotonin is thought now to have an antiepileptic effect. Antidepressant drugs like selective serotonin re-uptake inhibitors, i.e., fluoxetine, have proved to be useful in seizure control. Tryptophan (Trp), an essential amino acid, is the only brain precursor of serotonin, it competes with the other large neutral amino acids (LNAAs) for the carrier of blood-brain barrier (BBB). Our own data has shown a lowering of plasmatic LNAA levels in epileptic patients, on the basis of these results we could estimate a decrease of a 1/3 in the Trp brain intake rate in epileptics in respect to controls. Increasing plasmatic Trp levels increases brain serotonin synthesis. Trp and 5-hydroxytryptophan (5-HTP) were tested as an add on in epilepsy, but the clinical outcome was controversial. Free amino acids are not fully adsorbed by the gastro-intestinal system, furthermore LNAAs, and also 5-HTP is a LNAA, compete to cross the intestinal membrane for the same carrier, like for the BBB. The best way to increase the plasmatic Trp level is a protein rich in Trp and poor in the other LNAAs. Unfortunately Trp is a limited amino acid in proteins. We report the clinical results obtained by adding a whey protein to the antiepileptic therapy of drug-resistant epileptic patients: alpha-lactoalbumin, rich in Trp and poor in the other LNAAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood-Brain Barrier
  • Brain / metabolism*
  • Brain / pathology*
  • Drug Resistance*
  • Epilepsy / blood*
  • Epilepsy / metabolism*
  • Epilepsy / pathology*
  • Humans
  • Lactalbumin / metabolism
  • Models, Biological
  • Models, Theoretical
  • Pilot Projects
  • Seizures / prevention & control
  • Serotonin / metabolism*
  • Serotonin / pharmacology
  • Time Factors
  • Tryptophan / chemistry


  • Serotonin
  • Tryptophan
  • Lactalbumin