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Photosensitizing compounds in the treatment of psoriasis
H Hönigsmann1, A Tanew, J Brücke
1Department of Dermatology I, University of Vienna, Austria.
Abstract:
Photosensitizers were first used to treat psoriasis 15 years ago when the phototoxic reaction of psoralens and UVA was found to induce remissions of the disease. The effect of this reaction on DNA, particularly the formation of cross-links, was thought to be the decisive event. Strong cross-linking agents such as 8-MOP, TMP and 5-MOP are clinically effective whereas most compounds which produce only monofunctional adducts are virtually ineffective. Orally administered 8-methoxypsoralen (8-MOP) is the most widely used compound. 4,5',8-Trimethylpsoralen (TMP) is poorly absorbed from the intestine but has marked efficacy when applied topically. 5-MOP may be a useful alternative to 8-MOP because it is less erythemogenic and does not cause nausea. These three furocoumarins appear to be similar photochemically and may introduce similar risks. However, the photobiological properties of furocoumarins can be modified by altering one or more parts of the molecule. Such modifications might yield effective analogues with reduced cytogenetic hazards. Several psoralens and angular furocoumarins are being tested for effectiveness combined with fewest long-term side-effects, especially carcinogenesis. Encouraging preliminary results have been obtained with 7-methyl-pyridopsoralen and 4,6,4'-trimethylangelicin. Other important approaches to increasing the safety of photochemotherapy may be the use of different photoactivating wavelengths or the introduction of new classes of photosensitizers.
Insights
Photochemotherapy using psoralens and UVA light effectively treats psoriasis by inducing DNA cross-links. Researchers are developing safer psoralen analogues and new photosensitizers to minimize side effects like carcinogenesis.
Area of Science:
- Dermatology
- Photobiology
- Medicinal Chemistry
Background:
- Photochemotherapy, utilizing psoralens and ultraviolet A (UVA) light, has been a treatment for psoriasis for 15 years.
- The efficacy of this treatment is attributed to the phototoxic reaction, particularly DNA cross-linking induced by psoralens.
Purpose of the Study:
- To review the effectiveness of different psoralen compounds in psoriasis treatment.
- To explore strategies for developing safer photosensitizers with reduced long-term side effects, including carcinogenesis.
Main Methods:
- Clinical evaluation of psoralen derivatives, including 8-methoxypsoralen (8-MOP), 4,5',8-Trimethylpsoralen (TMP), and 5-MOP.
- Investigation into the photobiological properties and DNA interaction of various furocoumarins.
- Assessment of novel psoralen analogues and alternative photosensitizing agents.
Main Results:
- Strong DNA cross-linking agents like 8-MOP, TMP, and 5-MOP are clinically effective.
- Orally administered 8-MOP is widely used; TMP is effective topically. 5-MOP offers a less erythemogenic alternative to 8-MOP.
- Newer compounds like 7-methyl-pyridopsoralen and 4,6,4'-trimethylangelicin show promising results with potentially fewer side effects.
Conclusions:
- Modifying furocoumarin molecular structures can enhance therapeutic efficacy while reducing cytogenetic hazards.
- Ongoing research focuses on developing safer photochemotherapy options, including novel photosensitizers and alternative photoactivating wavelengths, to minimize risks like carcinogenesis.