Anthralin

Anthralin [1143-38-0] is acetylated using acetyl chloride in toluene and a pyridine catalyst to furnish 1,8-dihydroxy-lO-acetylanthrone [3022-61-5], an intermediate in the preparation of medications used in treating skin disorders, such as warts, psoriasis, and acne (38). Sugar esters can be similarly prepared from acetyl chloride under anhydrous conditions (39). 

Topical therapy is the initial drug treatment strategy for patients with mild to moderate psoriasis. It is estimated that approximately 70% to 80% of all patients with psoriasis can he treated adequately with use of topical therapy.1 Topical therapies include corticosteroids, coal tar products, anthralin, vitamin D3 analogues such as calcipotriol, retinoids such as tazarotene, and topical immunomodulators such as tacrolimus and pime-crolimus.18 Vitamin D3 analogues and topical retinoids all affect keratinocyte functions and the immune response. Currently, these are in wider use than is either anthralin or coal tar preparations. 

It has been proposed that anthralin-associated toxicity might be suppressed by systematic antioxidant administration [295]. The treatment of psoriatic patients with another drug dithranol resulted in a decrease in in vivo oxygen radical generation [296]. 

Anthralin possesses antiproliferative activity on keratinocytes, inhibiting DNA synthesis by intercalation between DNA strands. 

Because anthralin exerts its clinical effects at low cellular concentrations, therapy usually starts with low concentrations (0.1% to 0.25%) with gradual increases to higher concentrations (0.5% to 1%). Cream and ointment formulations are usually applied in the evening and allowed to remain overnight. 

Alternatively, short-contact anthralin therapy (SCAT) with application for 10 to 20 minutes of higher concentrations (1% to 5%) in water-soluble vehicles is effective with decreased local adverse effects. 

Anthralin products must be applied only to affected areas because contact with uninvolved skin may result in excessive irritation and staining, which usually disappear within 1 to 2 weeks of discontinuation. Staining of affected plaques indicates a positive response because cell turnover has been slowed enough to take up the stain. 

UVB light (290 to 320 nm) therapy is an important phototherapeutic intervention for psoriasis. The most effective wavelength is 310 to 315 nm, which led to development of a UVB narrowband light source, in which 83% of the UVB emission is at 310 to 313 nm. Topical and systemic psoriatic therapies are used adj unctively to hasten and improve the response to UVB phototherapy. Emollients enhance efficacy of UVB and can be applied just before treatments. Combining short-contact anthralin, calcipotriene, or topical retinoids to UVB may also improve results. However, topical application should be done after or at least 2 hours before UVB therapy because phototherapy can inactivate the topical product. UVB phototherapy may also be more effective when added to systemic treatments such as methotrexate and oral retinoids. 

Mannisto and coworkers (1984) have published a series of articles on the dermal toxicity of the anthralins in the minipig. In one experiment, 24 sites per minipig were used to assess the acute dermal irritation of various concentrations to four different chemicals per site. The range of concentrations tested permitted them to calculate the median erythema concentration and median irritation concentrations with relatively... 

In a second experiment (Hanhijarvi, Nevalainen, and Mannisto, 1985), the chronic, cumulative dermal effects of anthralin chemicals were studied in minipigs. Using only 12 animals, they were able, by having 32 sites per animal, to study the effects of two different chemicals (dithranol and butantrone both anthralins) in three different formulations at three different concentrations each. The protocol also included observations for systemic toxicity, clinical laboratory measurements, plasma drug analyses, and gross and histopathological examinations. 

Hanhijarvi, H., Nevalainen, T. and Mannisto, P. (1985). A six-month dermal irritation test with anthralins in the Gottinger miniature swine. Arch. Toxicol, 8 (Suppl.) 463 168. 

Mannisto, R, Havas, A., Haasio, K., Hahnijarvi, H. and Mustakallio, K. (1984). Skin irritation by dithranol (anthralin) and its 10-aceyl analogues in three animal models. Contact Dermatitis 10 140-145. 

Four anthralin (Anthra-Derm ) ointments are available which contain a. 1000 /rg/g... 

Four anthralin ointment (Anthra-Derm ) preparations are available containing 0.1, 0.25, 0.5, and 1.0% w/w active ingredient. Express these concentrations in terms of mg/g. 

Anthralin (59), used clinically as an antipsoriatic, inhibited human ISN (7 /zM) the oxidation products of (59) (the corresponding quinone and dimer) were not active [164]. A non-specific antioxidant effect was suggested, since co-oxidation of LTB4 and mouse ear 12-LO were inhibited at similar concentrations [165]. However, some other phenolic polycyclic aromatic compounds appear more specific in their actions. 

Anthralin (Anthra-Derm) [Keratolytic Dermatologic Agent]... 

Anthralin (Anthra-Derm) is a potent reducing agent whose mechanism of action is unknown. It is approved for the treatment of psoriasis and also may be helpful in alopecia areata. The major toxicides are discoloration of skin, hair, and nails and irritant dermatitis. 

Contraindications Acute psoriasis where inflammation is present, erythroderma, hypersensitivity to anthralin... 

Mouse skin Phorbol esters (croton oil) Anthralin Cigarette smoke condensate Dihydroteleocidin (fungal product) 7-Bromomethylbenz[a]anthracene UV light Wounding... 

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