Inhibition of prostaglandin generation in the rabbit brain in-vivo by AD-1590, a non-steroidal anti-inflammatory agent with potent antipyretic activity.
The inhibition of prostaglandin generation by AD-1590 was investigated in the rabbit brain in-vivo. AD-1590 (0.4 mg kg-1 i.v.) markedly prevented both the increases in body temperature and PGE2 level in cerebrospinal fluid (CSF) caused by i.v. injection of lipopolysaccharide. On the other hand, 2,4-dinitrophenol (20 mg kg-1 i.v.)-induced hyperthermia, which was not affected by AD-1590, was not accompanied by an increase in PGE2 level in CSF. When injected intracerebroventricularly, AD-1590 dose-dependently inhibited the hyperthermia caused by arachidonic acid given by the same route; its ED50 was 1.6 micrograms compared with about 35 micrograms for indomethacin. From these results, it is suggested that AD-1590 is more active than indomethacin in suppressing prostaglandin synthetase in rabbit brain.
Nakamura
H
H
Yokoyama
Y
Y
Motoyoshi
S
S
Seto
Y
Y
Kadokawa
T
T
Shimizu
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D003990:Dibenzoxepins / Q000494:pharmacology*; D015232:Dinoprostone; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000134:cerebrospinal fluid; D011817:Rabbits
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D003990:Dibenzoxepins; D011453:Prostaglandins; D011458:Prostaglandins E; D016718:Arachidonic Acid; C040006:bermoprofen; D015232:Dinoprostone; D007213:Indomethacin