Dioxopromethazine-induced photoallergic contact dermatitis followed by persistent light reaction.

BACKGROUND: Although photosensitivity after photoallergy to topical phenothiazine antihistamines is well known, there have been no previous reports of dioxopromethazine inducing this phenomenon. OBJECTIVE: A housewife used 0.5% dioxopromethazine in Prothanon gel for palpebral pruritus and developed severe dermatitis of the lower eyelids with spread to the sun-exposed areas. METHODS: The minimal erythema doses and the minimal infiltrate doses for ultraviolet A (UVA) and ultraviolet B (UVB) were established before photopatch testing and at intervals up to 497 days thereafter. Test sites were read up to 144 hours after irradiation. Photopatch testing was performed with Prothanon gel, dioxopromethazine hydrochloride 0.001% to 0.5%, and the standard photopatch test tray (Hermal/Trolab). For patch testing, various series of the German Contact Dermatitis Group were applied. RESULTS: Minimal erythema doses for UVA were diminished before photopatch testing and at intervals up to 500 days after Prothanon gel was discontinued. Exposure to UVB provoked abnormal delayed infiltrated reactions. Clinically the photosensitivity persisted within this period. Photoallergic reactions were seen with Prothanon gel, dioxopromethazine hydrochloride 0.005% to 1.0%, and promethazine hydrochloride 0.1%. The patient gave positive patch test reactions to various fragrance materials, balsam of Peru, costus oil, and propylene glycol. CONCLUSION: Because topical dioxopromethazine may cause photoallergic contact dermatitis followed by long-lasting photosensitivity even after contact has been discontinued, its withdrawal from the market is recommended.

Bioinorganic study on [Fe(promethazine)2H2O Cl]2+ complex.

The coordination chemistry of iron (III) is the environment of an antihistaminic drug, promethazine has been explained to include a low spin, six-coordinate complex [Fe(Prometha)2(H2O) Cl] Cl2. Metaldrug interaction in vitro in aqueous KCl phase was studied polarographically at physiological pH and temperature. On the basis of elemental, magnetic, conductometric, IR, UV-visible, NMR spectroscopic analysis it is concluded that in solid phase two promethazine molecules with their N,N donor sites encompass the metal. Mass spectral study on the complex confirms that one of the three chlorides is involved in the coordination. The respective changes in the antihistaminic activity of the drug as a result of complexation has been determined and a possible mechanism is suggested.

Initial nociceptive sensitization in carrageenin-induced rat paw inflammation is dependent on amine autacoid mechanisms: electrophysiological and behavioural evidence obtained with a quaternary antihistamine, thiazinamium.

We have studied the ability of a quaternary antihistamine, thiazinamium, to inhibit the nociceptive sensitization that occurs early, during the first hour, following intraplantar injection of the polysaccharide carrageenin in the rat. Parallel studies were performed with an electrophysiological model (changes in responsiveness of ventro-basal thalamic cells driven by noxious stimulation of the paws), and a behavioural test (changes in threshold stimulus necessary to elicit vocalization by gradually increased pressure to the paws). When thiazinamium was given intravenously 10 min before carrageenin, no sensitization due to inflammation was found in either test. By contrast, when thiazinamium was administered 20 min after carrageenin, there was a clear sensitization in both tests that did not differ from that found in animals not treated with the antagonist. Paw oedema was also slightly decreased by pretreatment with thiazinamium. These results suggests that early inflammatory sensitization of peripheral nociceptors is mainly dependent on an initial release of histamine (and/or serotonin, since thiazinamium could also have some antiserotoninergic activity).