The Scripps Research Institute

Steven J Henriksen

Richard A Lerner

Dale L Boger

Chi-Huey Wong

J Gregor Sutcliffe

Luis De Lecea

George R Siggins

Gary E Siuzdak

Ben Cravatt

The present invention relates generally to nucleic acids encoding a novel neuropeptide designated cortistatin. The cortistatin nucleic acids, proteins and polypeptides thereof along with anti-cortistatin antibodies are useful in both screening methods, diagnostic methods and therapeutic methods related to modulation of sleep and disorders thereof.

Antibodies to cortistatin: neuropeptides, compositions and methods

Cortistatin: neuropeptides

Inhibitors of oleamide hydrolase, responsible for the hydrolysis of an endogenous sleep-inducing lipid (1, cis-9-octadecenamide) were designed and synthesized. The most potent inhibitors possess an electrophilic carbonyl group capable of reversibly forming a (thio) hemiacetal or (thio) hemiketal to mimic the transition state of a serine or cysteine protease catalyzed reaction. In particular, the tight binding .alpha.-keto ethyl ester 8 (1.4 nM) and the trifluoromethyl ketone inhibitor 12 (1.2 nM) were found to have exceptional inhibitory activity. In addition to the inhibitory activity, some of the inhibitors displayed agonist activity which resulted in the induction of sleep in laboratory animals.

Inhibitors of oleamide hydrolase

Sleep may be induced by administration of fatty acid primary amides, including cis-9,10-octadecenoamide. Furthermore, sleep deprivation may be assayed by analyzing cerebrospinal fluid with respect to the presence of fatty acid primary amides, including cis-9,10-octadecenoamide. The presence of cis-9,10-octadecenoamide in cerebrospinal fluid is correlated with comparative sleep deprivation.

Method for sleep induction

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Solana Beach, CA, United States of America

Steven J Henriksen