Tiopinac displayed marked anti-inflammatory activity when given p.o. in rat models of acute and chronic
inflammation. It inhibited
carrageenan-induced paw
edema (40 x
phenylbutazone), and cotton-pellet-induced
granuloma (0.8 x
indomethacin). In an 18-day test,
tiopinac prevented the development of adjuvant-induced
arthritis (10-15 x
naproxen) and had similar activity versus pre-induced
arthritis.
Tiopinac exhibited antiphlogistic activity in adrenalectomized rats. It did not have
corticosteroid activity. Depending upon the type of
analgesic test used, the potency of
tiopinac varied. When given p.o. it inhibited
phenylquinone-induced writhing in the mouse and rat (respectively 16 and 10 x
aspirin). In contrast,
tiopinac had approximately 10 times the potency of
indomethacin in increasing the pain threshold when yeast-inflamed paws were compressed. The pain threshold of the noninflamed paw was not increased.
Tiopinac was highly active versus
pain induced by flexing the adjuvant arthritic-inflamed paw (greater than or equal to 1000 x
aspirin). It was inactive in the mouse hot-plate test in which
opiate-like agents are active.
Tiopinac, p.o., lowered yeast-induced
pyrexia (130 x
aspirin).
Tiopinac did not have significant cardiovascular or CNS activity. Whereas the Ed50 versus
adjuvant arthritis in rats was 0.1 mg/kg/day p.o., rats tolerated up to 20 mg/kg/day p.o. in the 8-day cotton-pellet test. Lack of
anorexia and
emesis in dogs with up to 30 mg/kg p.o. and mild oral activity in producing gastric erosion in acute and subacute studies in rats suggests that
tiopinac may have relatively little gastrointestinal irritating activity.