Tenidap is a new
anti-rheumatic agent which has clinical properties characteristic of a disease modifying
drug combined with acute antiinflammatory and
analgesic activity. This paper details
tenidap's
cyclooxygenase (COX) inhibitory activity and the resulting pharmacological properties in experimental animals.
Tenidap inhibited
calcium ionophore-stimulated
prostaglandin D2 synthesis by rat basophilic
leukemia cells (COX-1) with an IC50 of 20 nM. In two different in vitro human test systems,
tenidap inhibited COX-1 activity more potently than COX-2, although the relative potency ratio (COX-1/COX-2) differed markedly between the two systems.
Tenidap inhibited the COX pathway when added to human blood in vitro (IC50, 7.8 mu M) and when administered orally to monkeys, rats and dogs (at 5, 2.5 and 10 mg/kg p.o., respectively) and COX activity measured ex vivo in blood collected 2 to 4 hours post dose. After
oral administration to rats,
tenidap inhibited
carrageenan-induced paw
edema with an ED50 of 14 mg/kg and inhibited the
glucocorticoid-resistant UV
erythema in guinea pigs with an ED50 of 1.4 mg/kg. It retained antiinflammatory activity in adrenalectomized rats indicating that this property is independent of adrenal stimulation.
Oral administration of
tenidap inhibited the development of adjuvant-induced
polyarthritis in the rat and exhibited antinociceptive activity in the murine
phenylbenzoquinone and rat
acetic acid abdominal constriction tests. These data indicate that
tenidap is an effective antiinflammatory and
analgesic agent in animal models. These
cyclooxygenase-dependent pharmacologic activities do not explain
tenidap's disease modifying anti-arthritic properties but add a useful symptom modifying component to its clinical profile.