"ll 1 lNsntum @ mEScnppsRnsnencH 10666North Torey PinesRod I^ato lh, Ql ifon ia 92037 6 19.455.9100 Telephone For information: RobinB. Goldsmith (619)5s4-8134 Embargoby Sciencez Wire servicesandbroadcastnews, June8, 1995,3:00p.m. Pacifictime Print media,June9, 1995 #060995 Scripps Scientists Identify a Novel Lipid with Potential Sleep-Modulating ProPerties La Jolla, CA. June9, t995 - Researchersat The ScrippsResearchInstitute (TSRI) have isolated, characterizedand identified a novel moleculeof the primary amide family of lipids that has been shown to have sleep-inducingpropertiesin animal models. The investigators' work, publishedtn Science,suggeststhat a new, natural sourcefor a sleep modulating substancemay be at hand. The research,conductedby TSRI's departmentsof chemistry and neuropharmacology, entailed extracting the cerebrospinalfluid (CSF) of sleep-deprivedcats and subjectingit to modern analytical chemical techniquesto ascertainthe exact molecular structureof this molecule. was determinedby mass The structure of the compound,cis-9,l0-octadecenoamide, spectrometry,nuclear magneticresonancespectroscopy,infrared spectroscopy,gas chromatography,thin layer chromatographyand chemicaldegradationprocedures.This compoundand other fatry acid primary amideswere identified as natural constituentsof the cerebrospinalfluid of cat, rat, and man, indicating that thesecompoundscomposea distinct family of brain liPids. -more- Page2- ScrippsScientistsldentify a Novel Lipid was foundto be the only moleculethat A syntheticanalogueof the cis-9,10-octadecenoamide propertieswhen injectedinto rats.Accordingto StevenJ. exhibitedpotentsleep-inducing Henriksen,Ph.D.,the chief TSRI sleepphysiologyinvestigatoron the six-memberteam(see below), "The syntheticprimary amideput the rats to sleepin a remarkablynaturalmanner. The injections were given to the rats at the time when they would normally be awakeand the sleepthat was producedwas architecturallyvery similar to their normal sleepcycling." Aside from the potential ramificationsfor sleepmanipulationresearch,the TSRI study suggeststhat the fatty acid primary amidesmay representa new classof biological signaling molecules;that is, chemicalcompoundsthat play a part in the cascadeof eventsthat evolve when a molecule attachesto a cell membrane. The TSRI findings representthe latestresearchin the centuriesold searchfor safesleepinducing substances.While much researchwill needto be doneon the primary amides, includinglooking morecloselyat othermembers'ofthe lipid family andtheir long-term effect on circadianrhythms,the TSRI researchmay well be a major stepforward in understandingthe cellular processesunderlyingsleep. Other membersof the TSRI researchteamwere BenjaminF. Cravatt,OscarProspero-Garcia M.D., Ph.D.,Gary Siuzdak,Ph.D.,Dale L. Boger,Ph.D.,andRichardA. Lerner,M.D. ###