Chlorpromazine Photosensitivity in Mice: Its Action Spectrum and the Effect of Anti-Inflammatory Agents

Abstract

SUMMARY.— The photosensitizing action spectrum of chlorpromazine (CP) has been investigated in hairless mice. Our results suggest that CP photosensitivity in this animal has a broad action spectrum in the longwave u.v. spectrum, viz. from 330 to 370–380 nm., with peak activity at wavelengths just above normal sunburn wavelengths. In other words we could establish photosensitization activity of the drug at wavelengths which it is known to absorb that are longer than about 320 nm.; we were unable to demonstrate a lowering of threshold response in the presence of the drug when normal sunburn wavelengths were used. Both soya bean trypsin inhibitor and e‐amino‐n‐caproic acid inhibited the specific photosensitivity reactions of immediate or early onset, due to CP. This result suggests that the reaction may be mediated through the action of a plasmin or “protease‐polypeptide” system. It is tentatively suggested that the mediators causing the normal sunburn reaction may differ from those causing CP photosensitivity.

The Pattern of Fibrinolytic Activity in Human Skin Following Exposure to Middle‐wavelength Ultraviolet Light or Psoralen and Long‐wave Ultraviolet Light

“…The mechanism of this increase in the upper dermal activity is explained by the possibility that the release of Plg-A from the upper dermal vessel walls may be stimulated by psoralen and irradiation with UV A, which penetrate into the upper dermis (15). These results of the present study support the ideas of Hunter et al (16) that the drug photosensitized skin reaction to UVA may be mediated through the action of plasmin in' the early stages, because aaminocaproic acid; an antifibrinolytic agent, produced a definite reduction in the early reaction (up to 6 hours of UVA irradiation) from chlorpromazine photosensitization in mice. The activity in the upper dermis decreased gradually after appearance of PUV A erythema and was absent at 72-96 hours, when PUV A erythema was maximal.…”

Irreversible Photobinding to Skin Constituents After Systemic Administration of Chlorpromazine to Wistar Rats

“…It is noteworthy that maximal binding can be produced with 370 nm light whereas CPZ has its maximum absorption at 305 nm. These results correspond with the photosensitivity action spectrum established by Hunter et al (1970). They found that CPZ had an action spectrum from 330 to 370-380 nm in hairless mice.…”

“…These side effects were studied in in vivo experiments with mice. Erythema and oedema after administration of CPZ and exposure to UVA light were shown by Hunter et al (1970), Miyachi and Takigawa (1983) and Ljunggren and Moller (1977a), and photoallergic contact dermatitis to CPZ in mice was described by Maguire et al (1982).…”

The anatomical distribution of sunlight

“…This also applies to the action spectra for skin lesions in polymorphic light eruption and probably in photosensitivity by certain drugs. In these cases the long-wave limit of the polysulphone film is a little too short since polymorphic light eruption patients have been shown to be photosensitive to a wide spectrum (Magnus, 1964;Frain-Bell et al, 1973) and the phenothiazine derivative, chlorpromazine, was shown to be photoactive in hairless mice up to 400 nm (Hunter, Bhutani & Magnus, 1970). Table i shows that if the dose on the vertex is taken as 100%, that on approximately vertical surfaces of the body is about 50%.…”