OCULAR HYPOTENSION INDUCED BY TOPICAL DOPAMINERGIC DRUGS AND PHOSPHODIESTERASE INHIBITORS

The aim of this work was to investigate the ocular hypotensive activit y of some topically administered cAMP-phosphodiesterase inhibitors alo ne and in combination with dopaminergic compounds. Experiments were pe rformed with ocular normotensive rabbits and during transitory induced ocular hyper- or hypotension. An ocular hypotensive effect was observ ed after instillation of aminophylline, dyphylline, pentoxifylline, ca ffeine, and iso-caffeine, but not following topical hydroxypropyl-1,3- dimethylxanthine. Dopaminergic compounds were also studied in order to be combined with phosphodiesterase inhibitors as ocular anti-hyperten sive treatment. Significant ocular hypotensive activity was observed a fter topical application of trifluperidol, fluphenazine, thiothixene, and the S(-) enantiomer of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3 -PPP). Of the cAMP-phosphodiesterase inhibitors that were tested, pent oxifylline was the most interesting compound, with good ocular toleran ce, significant reduction in intra-ocular pressure, and potential reti nal microvascular benefits. After allowing adequate time for pentoxify lline to reach its maximal activity, trifluperidol or S(-)-3-PPP was a lso instilled. A more pronounced ocular hypotensive effect was then ob served. The findings of this study may suggest that administration of eye-drops combining drugs acting by separate ways on second messengers involved in the regulation of intra-ocular pressure (e.g. cyclic AMP) could be used to reduce intra-ocular pressure during glaucoma.