Further studies on the endogenous serotonin-uptake-inhibitor-like substances in the human cerebrospinal fluid.

The properties of endogenous substances that inhibit 5HT uptake in human cerebrospinal fluid (CSF) were investigated. Human CSF was loaded onto a Sephadex G-25 column, and each fraction was tested for its ability to inhibit [3H]paroxetine binding in monkey brain preparations. We found four different inhibitory peaks with respective molecular weights (M.W.) of > 12400, 2000 and two of < 1350. The third and fourth peaks (F-3, F-4: < 1350 M.W.) of inhibitory activity were determined to consist of some monoamines (5HT, etc.) or their metabolites (5HIAA, etc.) and other unidentified compounds by using an HPLC-electrochemical detector. The second peak (F-2, M.W. about 2000) displaced [3H]paroxetine binding noncompetitively (decreased Bmax and did not change Kd) and inhibited [3H]5HT uptake noncompetitively (decreased Vmax and did not change Km), but had no effect on either [3H]norepinephrine uptake or [3H]dopamine uptake. These results suggest that the endogenous substances that selectively inhibit 5HT uptake are present in human CSF as low molecular weight compounds.