Ocular and systemic disposition of the dopamine agonist N-0437 in monkeys after ocular administration

Abstract

The ocular and systemic disposition of the new dopamine agonist 2-( N-propyl- N-2-thienylethylamino)-5-hydroxytetralin (N-0437) was investigated in conscious monkeys after ocular administration of 0·56 mg N-0437. HCl (corresponding to 0·50 mg free base), containing 200 μCi [ 3H]N-0437, into the right eye. After killing the animal, the eyes were removed and several eye tissues were dissected and assessed for their content of radioactivity. In the treated eye, the iris contained by far the highest concentration of radioactivity, while in the untreated eye the lower conjunctiva, the iris the ciliary body and the choroid possessed the highest levels of radioactivity. In all dissected eye tissues, a substantially higher concentration of radioactivity was established for the treated eye compared to the untreated eye, except for the vitreous in which for both eyes about an equal concentration was measured. This result suggests the presence of a systemic transport, which was confirmed by the occurrence of bradycardia, starting immediately after ocular application of the drug and lasting for about 1·5 hr. As the total amount of radioactivity in both eyes 7 hr after ocular dosing is very low (0·3–0·5% of the dose), one can conclude that N-0437 is almost completely taken up into the general circulation. The radioactive measurements of bile and urine samples collected up to 7 hr after administration revealed that the elimination of N-0437 and its metabolites is very fast, with the urinary excretion (35% of the dose) slightly higher than to the biliary one (31% of the dose).