Brain uptake of radiolabeled N‐oleoyl‐dopamine in the rat

Abstract N ‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N ‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [ 3 H] N ‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [ 3 H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [ 3 H] N ‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [ 3 H]dopamine. Intravenous injections of [ 3 H] N ‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [ 3 H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N ‐oleoyl‐dopamine in the brain following injections. We conclude that N ‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N ‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N ‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc.