N-docosahexaenoyl, 3 hydroxytyramine: a dopaminergic compound that penetrates the blood-brain barrier and suppresses appetite.
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.
Shashoua
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Research Dept. Neuromedica Inc., Cambridge, MA 02139, USA.
Hesse
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GW
D000818:Animals; D001067:Appetite Depressants / Q000493:pharmacokinetics* / Q000494:pharmacology; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D004281:Docosahexaenoic Acids / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D015259:Dopamine Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution
D001067:Appetite Depressants; D002250:Carbon Radioisotopes; D015259:Dopamine Agents; D004337:Drug Carriers; C099171:NMI 8739; D004281:Docosahexaenoic Acids; D004298:Dopamine