The exact mechanism of action of methoxsalen with the
epidermal melanocytes and keratinocytes is not known. Psoralens given orally
are preferentially taken up by epidermal cells (Artuc et al, 1979)1.
The best known biochemical reaction of methoxsalen is with DNA. Methoxsalen, upon
photoactivation, conjugates and forms covalent bonds with DNA which leads to
the formation of both monofunctional (addition to a single strand of DNA) and
bifunctional adducts (crosslinking of psoralen to both strands of DNA)
(Dall'Acqua et al, 1971)2. Reactions with proteins have also been
described (Yoshikawa et al, 1979)3.
Methoxsalen acts as a photosensitizer. Topical
application of this drug and subsequent exposure to UVA, whether artificial or
sunlight, can cause cell injury. If sufficient cell injury occurs in the skin
an inflammatory reaction will result. The most obvious manifestation of this
reaction is delayed erythema which may not begin for several hours and may not
peak for 2 to 3 days or longer. It is crucial to realize that the length of
time the skin remains sensitized or when the maximum erythema will occur is
quite variable from person to person. The erythematous reaction is followed
over several days or weeks by repair which is manifested by increased
melanization of the epidermis and thickening of the stratum corneum. The exact
mechanics are unknown but it has been suggested that melanocytes in the hair follicles
are stimulated to move up the follicle and to repopulate the epidermis.
(Ortonne, et al, 1979)4
1. Artuc, M.; Stuettgen, G.; Schalla, W.; Schaefer, H.;
Gazith, J.: Reversible binding of 5- and 8- methoxypsoralen to human serum
proteins (albumin) and to epidermis in vitro; Brit. J. Dermat., 101, pp. 669-677
2. Dall'Acqua, F.; Marciani, S.; Ciavatta, L.;
Rodighiero, G.: formation of interstrand cross-linkings in the photoreactions
between furocoumarins and DNA; Z Naturfors ch (B), 26, pp. 561-569 (1971).
3. Yoshikawa, K.; Mori, N.; Sakakibara, S.; Mizuno, N.;
Song, P.: Photo-Conjugation of 8- methoxypsoralen with Proteins; Photochem
& Photobiol, 29, pp. 1127-1133 (1979).
4. Ortonne, J. P.; MacDonald, D.M.; Micoud, A.; Thivolet,
J.: PUVA-induced repigmentation of vitiligo: a histochemical (split-DOPA) and
ultra-structural study; Brit. J. Dermat., 101, pp. 1-12 (1979).