Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors.
The aim of this work was to investigate the ocular hypotensive activity of some topically administered cAMP-phosphodiesterase inhibitors alone and in combination with dopaminergic compounds. Experiments were performed with ocular normotensive rabbits and during transitory induced ocular hyper- or hypotension. An ocular hypotensive effect was observed after instillation of aminophylline, dyphylline, pentoxifylline, caffeine, 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-hypertensive treatment. Significant ocular hypotensive activity was observed after 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, pentoxifylline was the most interesting compound, with good ocular tolerance, significant reduction in intra-ocular pressure, and potential retinal microvascular benefits. After allowing adequate time for pentoxifylline to reach its maximal activity, trifluperidol or S(-)-3-PPP was also instilled. A more pronounced ocular hypotensive effect was then observed. 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.
Hariton
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Ciba-Vision Ophthalmics, International Ophtha R&D, Bülach, Switzerland.
D000287:Administration, Topical; D000818:Animals; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D015814:Ocular Hypotension / Q000139:chemically induced*; D009883:Ophthalmic Solutions; D010431:Pentoxifylline / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D013237:Stereoisomerism; D014272:Trifluperidol / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D015259:Dopamine Agents; D009883:Ophthalmic Solutions; D010726:Phosphodiesterase Inhibitors; D010880:Piperidines; D014970:Xanthines; C026539:preclamol; D005947:Glucose; D014272:Trifluperidol; D010431:Pentoxifylline