TENIDAP, A STRUCTURALLY NOVEL DRUG FOR THE TREATMENT OF ARTHRITIS - ANTIINFLAMMATORY AND ANALGESIC PROPERTIES

Tenidap is a new anti-rheumatic agent which has clinical properties ch aracteristic of a disease modifying drug combined with acute antiinfla mmatory and analgesic activity. This paper details tenidap's cyclo-oxy genase (COX) inhibitory activity and the resulting pharmacological pro perties in experimental animals. Tenidap inhibited calcium ionophore-s timulated prostaglandin D-2 synthesis by rat basophilic leukemia cells (COX-1) with an IC50 of 20 nM. In two different in vitro human test s ystems, tenidap inhibited COX-1 activity more potently than COX-2, alt hough the relative potency ratio (COX-1/COX-2) differed markedly betwe en the two systems. Tenidap inhibited the COX pathway when added to hu man blood in vitro (IC50, 7.8 mu M) and when administered orally to mo nkeys, rats and dogs (at 5, 2.5 and 10 mg/kg p.o., respectively) and C OX activity measured ex vivo in blood collected 2 to 4 hours post dose . After oral administration to rats, tenidap inhibited carrageenan-ind uced paw edema with an ED(50) of 14 mg/kg and inhibited the glucocorti coid-resistant UV erythema in guinea pigs with an ED(50) of 1.4mg/kg. It retained antiinflammatory activity in adrenalectomized rats indicat ing that this property is independent of adrenal stimulation. Oral adm inistration of tenidap inhibited the development of adjuvant-induced p olyarthritis in the rat and exhibited antinociceptive activity in the murine phenylbenzoquinone and rat acetic acid abdominal constriction t ests. These data indicate that tenidap is an effective antiinflammator y and analgesic agent in animal models. These cyclooxygenase-dependent pharmacologic activities do not explain tenidap's disease modifying a nti-arthritic properties but add a useful symptom modifying component to its clinical profile.