Preclinical activity profile of α-lactoalbumin, a whey protein rich in tryptophan, in rodent models of seizures and epilepsy

Epilepsy Res. 2011 Jun;95(1-2):60-9. doi: 10.1016/j.eplepsyres.2011.02.013. Epub 2011 Apr 1.


Purpose: To evaluate the potential anticonvulsant activity of α-lactalbumin (ALAC), a whey protein rich in tryptophan (TRP) relative to other large neutral amino acids (LNAAs), in rodent models of seizures and epilepsy.

Methods: The effects of ALAC administered per os were evaluated by standard protocols against audiogenic seizures in Genetic Epilepsy Prone Rats (GEPR-9 rats), maximal electroshock (MES)-induced seizures in rats, pilocarpine-induced seizures in mice, spontaneous chronic seizures in mice exposed to pilocarpine-induced status epilepticus (SE), and absence seizures in WAG/Rij rats. In some models, carbamazepine (CBZ) was included as an active control. Plasma TRP/LNAAs ratios were measured by GC-MS.

Results: Single doses of ALAC up to 500 or 6000 mg/kg were devoid of anticonvulsant activity in all models tested. Conversely, 5- and 12-day treatment with ALAC (250-1000 mg/kg/day) in GEPR rats reduced dose-dependently seizure scores and prolonged latency to clonus onset, with full persistence of the effect for up to 12h. ALAC (125-500 mg/kg/day for 15 days) protected against seizures induced by 250 mg/kg pilocarpine, but was less effective against higher pilocarpine doses. Similarly to CBZ, ALAC (125-500 mg/kg/day for 15 days) was also effective against spontaneous seizures in the post-pilocarpine SE model. ALAC (up to 6000 mg/kg/day for 12 days) did not prevent MES-induced seizures, although it reduced the duration of tonic extension at doses between 250 and 1000 mg/kg/day. Absence seizures in WAG/Rij rats were not significantly affected by ALAC. Plasma TRP/LNAAS ratios increased 2- to 3-fold after dosing with ALAC (250 mg/kg/day) for 7 and 14 days, respectively.

Conclusions: ALAC exerts significant protective activity against seizures in animal models, the effect being especially prominent against audiogenic seizures in GEPR-9 rats, seizures induced by low-dose pilocarpine in mice, and spontaneous seizures in mice exposed to pilocarpine-induced SE. This action is likely to be mediated by increased availability of TRP in the brain, with a consequent increase in 5-HT mediated transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / blood
  • Animals
  • Carbamazepine / administration & dosage
  • Carbamazepine / therapeutic use
  • Convulsants / toxicity
  • Drug Evaluation, Preclinical
  • Electroshock / adverse effects
  • Epilepsy / drug therapy*
  • Epilepsy, Reflex / drug therapy
  • Epilepsy, Reflex / genetics
  • Female
  • Lactalbumin / chemistry
  • Lactalbumin / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Pilocarpine / toxicity
  • Rats
  • Rats, Mutant Strains
  • Rats, Wistar
  • Seizures / drug therapy*
  • Serotonin / biosynthesis
  • Serotonin / physiology
  • Tryptophan / blood
  • Tryptophan / pharmacokinetics


  • Amino Acids
  • Convulsants
  • Pilocarpine
  • Serotonin
  • Carbamazepine
  • Tryptophan
  • Lactalbumin