Photooxidation Mechanism of Levomepromazine in Different Solvents

Abstract

Unwanted photoinduced responses are well-known adverse effects of most promazine drugs, including levomepromazine (LPZ, Levoprome ® or Nozinan ® ). This drug is indicated in psychiatry primarily for the treatment of schizophrenia and other schizoaffective disorders. Levomepromazine's particular sedative properties make it especially fit for use in psychiatric intensive care. Nevertheless, it is photolabile under UV-A and UV-B light in aerobic conditions resulting in the formation of its sulfoxide. The LPZ photochemistry in acetonitrile (MeCN) is completely different from that in methanol (MeOH) and phosphate buffer solutions (PBS, pH = 7.4). The major photoproduct in PBS and MeOH under aerobic conditions is levomepromazine sulfoxide (LPZSO), although the amount is considerably higher in the aqueous environment. The corresponding main photoproduct in MeCN could not be characterized. The destruction quantum yields of LPZ in PBS, MeOH and MeCN are 0.13, 0.02 and <10 À3 , respectively. It is further demonstrated that LPZSO does not form by the reaction of singlet oxygen with ground-state LPZ. This oxidation product is actually produced by the reaction of the cation radical of LPZ (LPZÁ + ) with molecular oxygen. This cation radical in turn, is produced by an electron transfer process between the 3 LPZ* and ground-state molecular oxygen.

Drug-Induced Photosensitivity—From Light and Chemistry to Biological Reactions and Clinical Symptoms

“…The drug molecule in triplet excited state or cation radicals may interact with molecular oxygen that results in singlet oxygen generation ( Figure 6 ). Moreover, reaction with oxygen leads to the production of oxidized products [ 160 , 161 ]. It has been reported that 2-chloroderivatives undergo dechlorination and then photoreduction or substitution.…”

Effect of chlorine substitution on triplet state structure of thioxanthone: A time‐resolved resonance Raman study

“…TX and its derivatives are of particular interest due to their interesting photochemical and photophysical properties . The triplet state of TXs are mainly responsible for their photochemical and photophysical reactions.…”

“…We have recently carried out a detailed vibrational study on the triplet state structure of the TX in the lowest excited triplet state . Even though attempts have been made to understand the triplet state photochemistry of CTX, till date, no systematic study has been reported concerning the structural aspects in both ground and lowest triplet excited states.…”