The anti-inflammatory and analgesic profile of 6,11-dihydrodibenzo-[b.e.]-thiepin-11-one-3-acetic acid (tiopinac).
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.
D000305:Adrenal Cortex Hormones / Q000502:physiology; D000700:Analgesics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001169:Arthritis, Experimental / Q000188:drug therapy; D002319:Cardiovascular System / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D003988:Dibenzothiepins / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D005260:Female; D006099:Granuloma / Q000188:drug therapy; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D051381:Rats
D000305:Adrenal Cortex Hormones; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003988:Dibenzothiepins; D011448:Prostaglandin Antagonists; C024834:tiopinac