Effects of the phthalazinone azelastine on epidermal metabolism after mechanical skin irritation.
In female NMRI mice, the phthalazinone azelastine was administered orally once daily over 7 days. The drug influenced the epidermal thymidine triphosphate and amino acid incorporation rates at doses between 1 and 5 mg/kg. In control mice, an epidermal hyperproliferation induced by abrasion of superficial epidermal layers was characterized by enhanced prostaglandin and leukotriene concentrations in epidermal homogenate, an increase in thymidine triphosphate and amino acid incorporation and an increase in epidermal thickness. In mice treated with 1 mg/kg azelastine HCl, this epidermal reaction was changed. Compared to controls, the increase in leukotriene concentration was diminished, and that of prostaglandins was enhanced. The incorporation of thymidine triphosphate and of amino acids as well as the epidermal thickness and the ratio cell count/epidermal thickness were increased in irritated skin of azelastine-treated mice. In conclusion, azelastine influences the epidermal metabolism in irritated and unirritated skin. Therefore, a beneficial role of this phthalazinone in the treatment of psoriasis and related skin disorders seems to be possible.
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, FRG.
M
M
Kietzmann
D
D
Lubach
M
M
Molliere
I
I
Szelenyi
D000284:Administration, Oral; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D017453:Dermatitis, Irritant / Q000188:drug therapy / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D010793:Phthalazines / Q000008:administration & dosage / Q000494:pharmacology*; D013189:SRS-A / Q000378:metabolism; D012885:Skinfold Thickness; D013942:Thymine Nucleotides / Q000378:metabolism
D015777:Eicosanoids; D006634:Histamine H1 Antagonists; D010793:Phthalazines; D013189:SRS-A; D013942:Thymine Nucleotides; C024157:thymidine 5'-triphosphate; C020976:azelastine