Possible therapeutic effect of trilostane in rodent models of inflammation and nociception.
BACKGROUND
Trilostane was identified in an in vivo screen of compounds in a lipopolysaccharide model of inflammation to support a repurposing effort. There is no previous documentation of any anti-inflammatory effects of trilostane.


OBJECTIVE
The aim of this study was to elucidate the novel pharmacologic activity of trilostane in a series of inflammation and nociception signal-finding models.


METHODS
Anti-inflammatory effects of trilostane were evaluated in lipopolysaccharide-induced systemic and lung inflammation models and in a 2,4-dinitrofluorobenzene-induced delayed-type hypersensitivity (DTH) model in the mouse ear. The analgesic activities of trilostane were evaluated in a hot plate nociception model as a function of paw-withdrawal latency and in the formalin-induced nociception model with a behavioral end point. In all studies, trilostane was administered 15 minutes before challenge. In the DTH model, the animals were given a second dose 24 hours after the first dose.


RESULTS
Trilostane inhibited tumor necrosis factor-α and monocyte chemoattractant protein-1 production in the lipopolysaccharide-induced systemic and pulmonary inflammation models. It also significantly reduced ear swelling in the 2,4-dinitrofluorobenzene-induced DTH model. In the hot plate nociception model, trilostane increased the latency of paw-licking behavior. Trilostane also significantly reduced the duration of pain behaviors in the late phase of the formalin-induced inflammatory pain model.


CONCLUSIONS
These signal-finding studies suggest that trilostane has novel anti-inflammatory and analgesic properties.
BioMed Valley Discoveries, Kansas City, Missouri.
David
D
Tung
Melior Discovery, Inc, Exton, Pennsylvania.
John
J
Ciallella
Melior Discovery, Inc, Exton, Pennsylvania.
Heather
H
Hain
BioMed Valley Discoveries, Kansas City, Missouri.
Peter H
PH
Cheung
BioMed Valley Discoveries, Kansas City, Missouri.
Saurabh
S
Saha
3 β-hydroxysteroid dehydrogenase; inflammation; trilostane