Archives of Dermatological Research

, Volume 281, Issue 1, pp 60–65 | Cite as

An attempt to reduce the photosensitizing potential of chlorpromazine with the simultaneous use of β- and dimethyl-β-cyclodextrins in guinea pigs

  • T. Hoshino
  • K. Ishida
  • T. Irie
  • K. Uekama
  • T. Ono
Original Contributions


The effects of topically applied β-cyclodextrin (β-CyD) and heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CyD) on photoallergic contact dermatitis due to chlorpromazine hydrochloride (CPZ) were investigated using the photomaximization technique in guinea pigs. From the gross and histological observations, the photosensitizing potential of CPZ with the simultaneous topical use of β-CyDs was significantly lower than that of CPZ alone. The alleviating efficacy of DM-β-CyD was greater than that of β-CyD. β-CyDs suppressed the penetration of CPZ into the skin through the formation of poorly skin-permeable complexes. In addition, β-CyDs inhibited (a) the photoinduced free radicals derived from CPZ in the isolated dry skin and (b) the in vitro photochemical binding of CPZ to bovine serum albumin. These observations suggest that β-CyDs suppress the photochemical reactions between CPZ and biological macromolecules present in the skin, resulting in the failure to form a photoantigen. The present results indicate that DM-β-CyD is particularly effective in alleviating photoallergic contact dermatitis due to CPZ.

Key words

Chlorpromazine β-Cyclodextrin Dimethyl-β-cyclodextrin Inclusion complex Photoallergic contact dermatitis Skin penetration Photochemical reactivity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Barratt MD, Brown KR (1985) Photochemical binding of photoallergens to human serum albumin: a simple in vitro method for screening potential photoallergens. Toxicol Lett 24:1–6Google Scholar
  2. 2.
    Bender ML, Komiyama M (1978) Cyclodextrin chemistry. Springer, Berlin Heidelberg New YorkGoogle Scholar
  3. 3.
    Chignell CF, Motten AG, Buettner GR (1985) Photo-induced free radicals from chlorpromazine and related phenothiazines: relationship to phenothiazine-induced photosensitization. Environ Health Perspect 64:103–110Google Scholar
  4. 4.
    Cronin E (1980) Contact dermatitis. William Clowes (Beccles), LondonGoogle Scholar
  5. 5.
    Epstein JH, Wintroub BU (1985) Photosensitivity due to drugs. Drugs 30:42–57Google Scholar
  6. 6.
    Epstein S (1968) Chlorpromazine photosensitivity: phototoxic and photallergic reactions. Arch Dermatol 98:354–363Google Scholar
  7. 7.
    Foussereau J, Benezra C, Maidbach H (1982) Occupational contact dermatitis: clinical and chemical aspects. Fyens Stiftsbogtrykkeri, Odense, DenmarkGoogle Scholar
  8. 8.
    Fukawa K, Ito Y, Ohbayashi S, Iwadate K, Irino O, Sawabe T (1982) A new method for the local irritation test. II. Skin irritation test for powder drugs. Yakugaku Zasshi 102:89–98Google Scholar
  9. 9.
    Ichikawa H, Armstrong RB, Harber LC (1981) Photoallergic contact dermatitis in guinea pigs: improved induction technique using Freund's complete adjuvant. J Invest Dermatol 76:498–501Google Scholar
  10. 10.
    Irie T, Otagiri M, Uekama K, Yoneda F, Kusu F, Takamura K (1983) Effects of cyclodextrins on the riboflavin-sensitized photooxidation of phenothiazine derivatives. Nippon Kagaku Kaishi 219–224Google Scholar
  11. 11.
    Ishida K, Hoshino T, Irie T, Uekama K (1988) Alleviation of chlorpromazine-photosensitized contact dermatitis by β-cyclodextrin complexations and their possible mechanism. Yakubutu Doutai 3:377–386Google Scholar
  12. 12.
    Kochevar IE (1979) Photoallergic responses to chemicals. Photochem Photobiol 30:437–442Google Scholar
  13. 13.
    Lovell CR, Cronin E, Rhodes EL (1986) Photocontact urticaria from chlorpromazine. Contact Dermatitis 14:290–291Google Scholar
  14. 14.
    Miyata T, Takahama K, Irie T, Uekama K (1988) Toxicological properties of phenothiazines. In: Gupta RR (ed) Bioactive molecules, vol 4. Phenothiazines and 1,4-benzothiazines. Chemical and biomedical aspects. Elsevier, Amsterdam, pp 665–703Google Scholar
  15. 15.
    Nomura S (1974) Occupational dermatoses and its medical control. Roken, TokyoGoogle Scholar
  16. 16.
    Okamoto H, Komatsu H, Hashida M, Sezaki H (1986) Effects of β-cyclodextrin and di-0-methyl-β-cyclodextrin on the percutaneous absorption of butylparaben, indomethacin and sulfanilic acid. Int J Pharm 30:35–45Google Scholar
  17. 17.
    Otagiri M, Uekama K, Ikeda K (1975) Inclusion complexes of β-cyclodextrin with tranquilizing drugs phenothiazines in aqueous solution. Chem Pharm Bull 23:188–195Google Scholar
  18. 18.
    Pitha J (1984) Biomedical applications of complexation agents/solubilizers. J Incl Phenom 2:477–485Google Scholar
  19. 19.
    Rosenthal I, Ben-Hur E, Prager A, Riklis E (1978) Photochemical reactions of chlorpromazine; chemical and biochemical implications. Photochem Photobiol 28:591–594Google Scholar
  20. 20.
    Satanove A (1965) Pigmentation due to phenothiazines in high and prolonged dosage. JAMA 191:263–268Google Scholar
  21. 21.
    Uekama K, Irie T (1987) Pharmaceutical applications of methylated cyclodextrin derivatives. In: Dominique Duchene (ed) Cyclodextrins and their industrial uses. Editions de Sante, Paris, France, pp 393–439Google Scholar
  22. 22.
    Uekama K, Otagiri M (1987) Cyclodextrins in drug carrier systems. Critical Rev Ther Drug Carrier Syst 3:1–40Google Scholar
  23. 23.
    Uekama K, Irie T, Hirayama F (1978) Participation of cyclodextrin inclusion catalysis in photolysis of chlorpromazine to give promazine in aqueous solution. Chem Lett 1109–1112Google Scholar
  24. 24.
    Uekama K, Irie T, Sunada M, Otagiri M, Iwasaki K, Okano Y, Miyata T, Kase Y (1981) Effects of cyclodextrins on chlorpromazine-induced haemolysis and central nervous system responses. J Pharm Pharmacol 33:707–710Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • T. Hoshino
    • 1
  • K. Ishida
    • 1
  • T. Irie
    • 1
  • K. Uekama
    • 1
  • T. Ono
    • 2
  1. 1.Faculty of Pharmaceutical SciencesKumamoto UniversityKumamotoJapan
  2. 2.Department of DermatologyKumamoto University, Medical SchoolHonjo, KumamotoJapan

Personalised recommendations