Memory enhancement mediated by the steroid sulfatase inhibitor (p-O-sulfamoyl)-N-tetradecanoyl tyramine.
The intent of this study was to determine whether altering the metabolism of neurosteroids via blockade of the enzyme, steroid sulfatase, could enhance memory retention in rats. The steroid sulfatase inhibitor p-O-(sulfamoyl)-N-tetradecanoyl tyramine (DU-14) was administered alone and in combination with the neurosteroid dehydroepiandrosterone sulfate (DHEAS) to rats which were then tested for the reversal of scopolamine-induced amnesia. A single 30 mg/kg IP dose of DU-14 produced a significant inhibition of steroid sulfatase activity in both brain (14.8%), and liver (85.2%) tissues, 24 hours following administration. In a passive avoidance test, DU-14 enhanced the reversal of amnesia by DHEAS. These results suggest that steroid sulfatase inhibition can potentiate the memory enhancing properties of DHEAS.
Li
P K
PK
Division of Pharmacology-Toxicology, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
Rhodes
M E
ME
Burke
A M
AM
Johnson
D A
DA
D000759:Adjuvants, Anesthesia / Q000633:toxicity; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D001192:Arylsulfatases / Q000037:antagonists & inhibitors*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003687:Dehydroepiandrosterone / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000633:toxicity; D043266:Steryl-Sulfatase; D014439:Tyramine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
C103321:4-O-(sulfamoyl)-N-tetradecanoyltyramine; D000759:Adjuvants, Anesthesia; D004791:Enzyme Inhibitors; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D012601:Scopolamine; D001192:Arylsulfatases; D043266:Steryl-Sulfatase; D014439:Tyramine