Biphasic dose-dependent effects of dopamine and involvement of dopamine autoreceptors on intra-ocular pressure in the rabbit.
1. This work was conducted to provide new data concerning the possible dose-dependent activity of dopamine (DA) after ocular instillation. Experiments were done in rabbits with normal intraocular pressure (IOP), or after transitory induced ocular hypertension in water-loaded animals. 2. In ocular normotensive animals, a biphasic dose-dependent activity is observed, with no significant effect for 0.001% and 0.003% DA, a decrease in IOP after 0.005% and 0.01% DA instillation, then an important increase in IOP at concentrations from 0.05% onwards. 3. During transitory ocular hypertension, this phenomenon was confirmed, with a marked ocular hypotensive activity for 0.01% DA, no effect after 0.005% DA, then an important ocular hypertension with 0.05% and 0.5% DA as compared to the control group (0.9% NaCl). 4. An immediate and similar ocular hypertensive effect with DA could be reproduced by a subsequent instillation at high concentration (1%), while the hypotensive activity induced at low concentration (0.01%) is followed by a long-lasting refractory period (about 18 h). 5. Such a dose-dependent biphasic effect was also observed with N-methyl-dopamine (NMDA) after ocular instillation. The effects of instilled dopaminergic compounds were tested and ocular hypotensive activities of the S(-)enantiomer of the DA analogues 3-(3-hydroxyphenyl)-N-propylpiperidine (3-PPP), and of thiothixene (TIX) were also demonstrated. 6. The possible relationships to DA1 and DA2 receptors of the dual effect is discussed.
Hariton
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Laboratoires Martinet, Pharmacology labs., Paris, France.
D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009798:Ocular Hypertension / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D011954:Receptors, Dopamine / Q000187:drug effects*; D013888:Thiothixene / Q000494:pharmacology
D015259:Dopamine Agents; D010880:Piperidines; D011954:Receptors, Dopamine; D016202:N-Methylaspartate; D013888:Thiothixene; C026539:preclamol; D004298:Dopamine