Photophysical studies on antimalarial drugs.

Area of Science:

• Pharmacology
• Photochemistry
• Ophthalmology

Background:

• Antimalarial drugs frequently cause phototoxic side effects affecting skin and eyes.
• These effects range from pigmentation changes to irreversible retinal damage and blindness.
• The underlying mechanisms of these phototoxic reactions remain largely unknown.

Purpose of the Study:

• To investigate the phototoxic mechanisms of common antimalarial drugs.
• To identify reactive intermediates and photophysical processes induced by light exposure in these drugs.

Main Methods:

• Irradiation of antimalarial drugs (amodiaquine, chloroquine, hydroxychloroquine, mefloquine, primaquine, quinacrine) with light (λ > 300 nm).
• Electron paramagnetic resonance (EPR) studies using a spin trap (5,5-dimethyl-1-pyrroline N-oxide).
• Laser flash photolysis to detect singlet oxygen production and quenching.

Main Results:

• EPR studies revealed various radical adducts (superoxide/hydroperoxyl, carbon-centered, nitrogen-centered) depending on the drug and solvent.
• Mefloquine, quinine, amodiaquine, and a quinacrine photoproduct generated singlet oxygen.
• Primaquine was unique in efficiently quenching singlet oxygen.

Conclusions:

• The study elucidates potential mechanisms for antimalarial drug-induced phototoxicity through the formation of reactive intermediates and singlet oxygen.
• Primaquine appears to have a different phototoxic profile compared to other tested antimalarials.
• Recommending protective measures against light exposure is crucial when administering these drugs, especially in high-intensity light regions.