N-docosahexaenoyl, 3 hydroxytyramine: a dopaminergic compound that penetrates the blood-brain barrier and suppresses appetite

Life Sci. 1996;58(16):1347-57. doi: 10.1016/0024-3205(96)00101-4.

Abstract

Fatty acids with varying chain lengths (2-22 carbon atoms long) and degrees of unsaturation (0-6 double bonds) were used to synthesize dopaminergic compounds for a study of the carrier mediated transport of dopamine (DA) to the brain. The most active carrier was the all cis C22:6 fatty acid [docosahexaenoic acid, (DHA)]which increased DA uptake through the blood-brain barrier by greater than 7.5 fold. The DHA-DA compound, NMI 8739, depressed the general locomotor activity of mice in a dose dependent manner. It also suppressed the appetite of Balb c mice and Charles River rats by 50% and 95% respectively at a dose of 10 mg/kg. Daily administration of NMI-8739 for a three week period did not induce tolerance. These results demonstrate DHA's potential for the carrier mediated transport of small molecules to the brain.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Appetite Depressants / pharmacokinetics*
  • Appetite Depressants / pharmacology
  • Blood-Brain Barrier*
  • Brain / metabolism
  • Carbon Radioisotopes
  • Docosahexaenoic Acids / chemical synthesis
  • Docosahexaenoic Acids / pharmacokinetics*
  • Docosahexaenoic Acids / pharmacology
  • Dopamine / analogs & derivatives
  • Dopamine / chemical synthesis
  • Dopamine / pharmacokinetics*
  • Dopamine / pharmacology
  • Dopamine Agents / pharmacokinetics*
  • Dopamine Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Carriers / chemical synthesis
  • Drug Carriers / pharmacokinetics
  • Mice
  • Mice, Inbred BALB C
  • Motor Activity / drug effects
  • Rats
  • Subcellular Fractions / metabolism
  • Tissue Distribution

Substances

  • Appetite Depressants
  • Carbon Radioisotopes
  • Dopamine Agents
  • Drug Carriers
  • NMI 8739
  • Docosahexaenoic Acids
  • Dopamine