Muramyl Peptide-Enhanced Sleep: Pharmacological Optimization of Performance.

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.