Muramyl Peptide-Enhanced Sleep: Pharmacological Optimization of Performance

The broad objective of this research is to develop the information needed to ascertain whether muramyl peptides MPs andor other endogenous sleep factors SFs may be useful as somnogenic agents. Several SFs have been identified that may be involved in the cascade of biomedical events involved in regulation of sleep, e.g. interleukin-1 IL1. Thus, we think it possible that new more effective somnogenic agents could be developed using MPs andor other putative SFs. In the second year of this contract six experiments were performed MP somnogenic activity relationships were determined. The preoptic area POA of the brain has been implicated in sleep regulation. Relationships between sleep and infectious disease are examined. Staphylococcus aureus greatly altered rabbit sleep patterns over the course of the infections. Endotoxin and its lipid A moiety are components of gram-negative bacteria that share with MPs the ability to induce increased IL1 production. Alpha-melanocyte-stimulating hormone aMSH, proopiomelanocortin-derived peptide which acts as a physiological inhibitor of some of IL1 actions, inhibited normal sleep and also antagonized IL1-enhanced sleep.