Prostaglandin E2 and its methyl ester reduce cataplexy in canine narcolepsy.
The effects of intravenous administration of prostaglandins (PGs) were investigated in genetically narcoleptic Doberman pinschers. The treatment of narcoleptic dogs with PGE2 and PGE2 methyl ester, but not PGD2 and PGD2 methyl ester, induced a dose-dependent reduction of canine cataplexy, a dissociated manifestation of rapid-eye-movement sleep. The effect was specific and not associated with any change in other behavior. Furthermore, the effect was long-lasting (up to 2 hr) and could not be explained by the acute cardiovascular changes seen after intravenous PG administration. PGE2 methyl ester, a lipophilic derivative of PGE2 with more central penetration than PGE2, was 4 times more potent than PGE2. These results indicate that PGE2 modifies cataplexy through a central effect and suggest that this prostaglandin may play a role in rapid-eye-movement sleep regulation.
Nishino
S
S
Sleep Disorders Center, Stanford University School of Medicine, Palo Alto, CA 94304.
Mignot
E
E
Fruhstorfer
B
B
Dement
W C
WC
Hayaishi
O
O
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002385:Cataplexy / Q000188:drug therapy / Q000503:physiopathology*; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D004283:Dog Diseases / Q000503:physiopathology*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009290:Narcolepsy / Q000503:physiopathology / Q000662:veterinary*; D012016:Reference Values; D012890:Sleep / Q000187:drug effects
C041324:prostaglandin E2 methyl ester; D015232:Dinoprostone