Priorities & Actions
Parkinson's Plan 2006
Parkinson's Matrix
Research Agenda

Research Resources
Animal Models
Antibody Resources
Clinical Research
Gene Therapy
Genetic Resources
Brain Banks Across the
   United States

Funding Research
Funding Announcements
Clinical Trials
Related Literature

Research Centers
NIH Intramural Research
Udall Centers of
   Excellence

Patient/Caregiver Information
Parkinson's Disease
PD Clinical Trials

Contact Us
My Privacy

NINDS is part of the
National Institutes of
Health

Download Adobe Reader

  Print-friendly version

   Email this page

Join our electronic mailing list

---

A number of compounds were identified as candidates for further study by the Committee to Identify Neuroprotective Agents in Parkinson's (CINAPS). Of these compounds, Minocycline, Creatine , CoQ10 and GPI 1485 have been selected for testing in the Neuroprotection Clinical Trial.

Modafinil

Modafinil may affect GABA or glutamate release, have neurotrophic activity or be responsible for cellular metabolism change. It is 90% metabolized by the liver, 60% protein bound in plasma, and is widely distributed through out issues. Modafinil is well tolerated in PD patients with side effects reported in narcolepsy clinical trials, such as headache, chest pain, nausea and diarrhea.

Scientific Rationale

• Unknown¹
• May affect GABA or glutamate release, have neurotrophic activity or change cellular metabolism (theories) ²

1. Aguirre, Neuroscience Lett 1999; 275:215-218
2. Jenner, Exp Brain Res 2000; 133:178-188

Animal Model Data

RODENT:

• Mice: 25 animals (in 4 groups, 2x2 design) received MPTP 40 mg/kg subcutaneous (sc) and modafinil 100 mg/kg intraperitoneal (IP) or saline at the same time as MPTP. After 7 days, animals were sacrificed. MPTP alone caused a 44% decrease in nigral neurons (both dopaminergic and non-dopaminergic) and modafinil prevented this decrease entirely¹
• Mice: mice administered MPTP 40 mg/kg sc were given 10-100 mg/kg of modafinil and modafinil was shown to protect against the MPTP-induced loss of nigrostriatal DA neurons.

PRIMATE

• Marmosets: 16 animals were divided into 4 groups in which all animals received MPTP 2 mg/kg sc daily for 5 days, with or without concurrent modafinil 10,30 or 100 mg/kg daily during MPTP and for 2 weeks after (+4 normal controls). Seven days after the end of modafinil treatment, animals were sacrificed. MPTP alone caused a 76% reduction in DA neurons in the SNpc. Treatment with 100 mg/kg of modafinil produced a significant (p<0.01) preservation in DA neurons (only a 23% reduction). This study also demonstrated that in 4 animals with 9 month old MPTP lesions, modafinil improved function (a symptomatic effect).

1. Aguirre, Neuroscience Lett 1999; 275:215-218
2. Fuxe, Exp Brain Res 1992; 88:117-130 (ABSTRACT ONLY)
3. Jenner, Exp Brain Res 2000; 133:178-188

Pharmacokinetics(including BBB penetration)

Modafinil is 90% metabolized by the liver, 60% protein bound in plasma. It is widely distributed throughout tissues and has a half-life of 15 hours. BBB penetration is presumed based on its CNS effects in humans. MD Consult, 2002

Safety/Tolerability in Humans

Modafinil is well-tolerated in doses up to 400 mg/day (200 mg/day is the max dose for narcolepsy).¹Twenty-one PD patients with sleepiness were given 200 mg/day of modafinil in a DB, PC, crossover manner with 3 weeks of treatment interleaved with a 1 week washout. Modafinil significantly decreased sleepiness with no effect on "ON" time. There were no adverse effects reported.² In narcolepsy clinical trials, adverse events were: headache, chest pain, nausea, diarrhea.¹

1. MD Consult, 2002
2. Adler, Neurology 2001; 56(suppl 3): A308 (ABSTRACT)

Drug Interaction Potential

• Induces CYP 3A4 (steroids, cyclosporine)
• Inhibits CYP 2C19 (phenytoin, diazepam)

Clinical Trial/Epidemiological Evidence in Human PD

N ONE

Last updated February 09, 2005