Evaluation in rats of the somnogenic, pyrogenic, and central nervous system depressant effects of muramyl dipeptide.
Muramyl dipeptide increased sleep during the dark-phase, but not the light-phase of the rats' sleep-awake cycle. This circadian variation may be due to the inability of MDP to increase sleep over the high baseline levels of sleep that occur during the light-phase. However, MDP was pyrogenic during the light-phase, indicating it was pharmacologically active. In the dark-phase, MDP was not pyrogenic, but when compared to concurrent vehicle-treated rats, rats treated with MDP did not demonstrate as great a fall in body temperature. At approximately equisomnogenic doses, MDP produced less potentiation of ethanol-induced loss of righting reflex than triazolam, indicating it produces less non-specific central nervous system depressant effects. These data indicate the possibility of a new generation of hypnotic agents derived from muramyl peptides.
Meltzer
L T
LT
Department of Pharmacology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105.
Serpa
K A
KA
Moos
W H
WH
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D012890:Sleep / Q000187:drug effects*; D014229:Triazolam / Q000494:pharmacology
D002492:Central Nervous System Depressants; D007375:Interleukin-1; D011453:Prostaglandins; D014229:Triazolam; D000431:Ethanol; D000119:Acetylmuramyl-Alanyl-Isoglutamine