An investigation of the ability of antipsoriatic drugs to inhibit calmodulin activity: a possible mode of action of dithranol (anthralin).
Epidermal calmodulin (CaM) has been reported to be elevated in psoriasis and to decrease following clearance of psoriasis with treatment. We set out to investigate whether any of the principle drugs used in the treatment of psoriasis had inherent CaM antagonist activity. Utilizing a CaM-activated phosphodiesterase we have demonstrated that even at very high concentrations, the systemic drugs etretinate, methotrexate, and 8-methoxypsoralen, and the topical agents hydrocortisone and crude coal tar showed minimal CaM inhibitory activity. Dithranol (anthralin), however, whether freshly prepared or oxidized, produced substantial inhibition of CaM activity and was demonstrated to be a potent competitive antagonist of CaM, suggesting another possible therapeutic mode of action of dithranol in psoriasis.
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D000875:Anthralin / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002417:Cattle; D003033:Coal Tar / Q000494:pharmacology; D005050:Etretinate / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D008727:Methotrexate / Q000494:pharmacology; D008730:Methoxsalen / Q000494:pharmacology; D010084:Oxidation-Reduction; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy*
D000873:Anthracenes; D002147:Calmodulin; D005050:Etretinate; D003033:Coal Tar; D010727:Phosphoric Diester Hydrolases; D008730:Methoxsalen; D000875:Anthralin; D006854:Hydrocortisone; D008727:Methotrexate