Accession Number : ADA186496

Title :   Muramyl Peptide-Enhanced Sleep: Pharmacological Optimization of Performance.

Descriptive Note : Annual rept. 1 Jun 86-31 May 87,

Corporate Author : TENNESSEE UNIV MEMPHIS DEPT OF PHYSIOLOGY AND BIOPHYSICS

Personal Author(s) : Krueger, James M

PDF Url : ADA186496

Report Date : 01 Jun 1987

Pagination or Media Count : 81

Abstract : Research dealt with the somnogenic actions of factors isolated from rabbit brain and human urine. We identified these substances an muramyl peptides (MPs) and subsequently showed that a simple chemical analog to these MPs, N-acetylmuramyl-L-alanyl-D-isoglutamine (or MDP for muramyl dipeptide) was also somnogenic. Our evidence indicated that MPs have the capacity to enhance SWS and several other laboratories had confirmed and extended that finding. The broad goal of the research is to develop information necessary for the evaluation of MPs as sedatives for military use. This year, five sets of experiments were performed with this goal in mind. The effects of MDP on rabbit rapid-eye movement sleep (REMS) and relationships between MDP-altered sleep and thermoregulation were investigated. The interaction of MDP with two drugs of military interest, amphetamine and eserine, was examined. We found that MDP could reverse amphetamine-induced insomnia but that MDP failed to reverse eserine-induced wakefulness. We found that O-acetylation of the 6-carbon of muramic acid enhanced somnogenic activity of an mp. Many MPs are also immune response modifiers as well as pyrogenic and somnogenic. We measured the somnogenic effects of MDP in conjunction with a biochemical measure of the host defense response, plasma copper. MPs can alter the production of cytrokines such as interleukin-1 and tumor necrosis factor. We showed that both recombinant DNA-derived interleukin-1 and tumor necrosis factor have the capacity to enhance SWS in rabbits.

Descriptors :   *HYPNOTICS AND SEDATIVES, *SLEEP, AMPHETAMINES, BIOCHEMISTRY, BLOOD PLASMA, BRAIN, CHEMICAL ANALOGS, COPPER, HUMANS, NECROSIS, NEOPLASMS, OPTIMIZATION, PRODUCTION, RABBITS, TEMPERATURE CONTROL, URINE

Subject Categories : Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE