Effects of the phosphodiesterase 4 inhibitor RPR 73401 in a model of immunological inflammation

The study was performed to investigate effects of the phosphodiesterase 4 inhibitor RPR 73401 [N-(3,5-dichloropyrid-4-yl)-3-cyclopentyl-oxy-4-methoxybenzamid] on an allergic skin reaction. To simulate an immunological inflammation, BALB/c mice were sensitized to dinitrochlorobenzene or toluenediisocyanate. At first, the abdominal skin was shaved and 50 mu l Freund's adjuvant were injected intracutaneously once. Then, the horny layer was removed by adhesive tape stripping and 100 mu l 0.5% dinitrochlorobenzene or 5% toluenediisocyanate were administered on the epidermis for 4 days. After repeated local treatment of the ear skin with 20 mu l 3% RPR 73401 or intraperitoneal administration of 1 and 5 mg/kg RPR 73401, 20 mu l 1% dinitrochlorobenzene or 0.5% toluenediisocyanate were given topically as a challenge. The vehicle controls showed a high increase in ear thickness over 48 h after challenge, whereas RPR 73401 administered on either route reduced this increase significantly. Nevertheless after topical administration, RPR 73401 had a longer lasting effect. These and other results may point to an indication for RPR 73401 in immunological dermatitis. (C) 2000 Elsevier Science B.V. All rights reserved.