Effects of xanthine derivatives on electroretinographic responsiveness

Abstract

In view of the use of synthetic propentofylline (PPF) as a protective agent in brain ischemia, its possible side effects on vision capacities have been explored by electroretinography in comparative experiments with theophylline. We used eyecup preparations of small-spotted dogfish sharks and of European eels, particularly suitable for long-lasting experiments. The drug exerted profound but reversible modifications of ERG records: (1) a dose-dependent increase of the amplitude and duration of the chemically isolated late receptor potential (LRP), (2) a partial unmasking of LRP, (3) a strong potentiation of the LRP-unmasking effect of low temperature, (4) a potentiation of light adaptation effects, and (5) a strong potentiation of the post-illumination hyperexcitability. The effects were explicable as due to a strong phosphodiesterase (PDE) inhibiting, cyclic guanosine monophosphate (cGMP) promoting, action of the drug. The effects were considerably stronger, or even of opposite sign, in comparison to those of the chemically related theophylline. PPF did not seriously affect the ERG c-wave originating in the pigment epithelium. The results suggested that the effects of PPF on vision may not seriously hamper the therapeutic use of the drug. They indicated, on the other hand, that PPF was a retinoactive drug of potential usefulness in the exploration of the complex biochemical events underlying visual transduction.