Muramyl peptides. Variation of somnogenic activity with structure.

Abstract

Sleep-promoting activities of muramyl dipeptide (MDP) (NAc-Mur-L-ala-D-isogln) and the naturally occurring muramyl peptide(s), factor S, have recently been demonstrated. Understanding of structural requirements for somnogenic activity was amplified. The effects of several analogs of MDP on rabbit slow-wave sleep are presented and the results are compared to the dose-response relationship for MDP. Some tentative conclusions as to structural requirements for somnogenic activity are presented; most notably, amidation of the free .gamma.-carboxyl of MDP and several of its analogs resulted in the loss of somnogenic activity. MDP also can induce febrile and immunostimulatory responses. Some analogs possess immunostimulatory and pyrogenic activity not not somnogenic activity, suggesting that these biological activities of muramyl peptides may, in part, be mediated by separate mechanisms.