Abstract
Phenylethylamine derivatives have been used topically for many years in ophthalmology. It is well known that many of these materials will lower intraocular pressure (IOP). Side-effects produced by the drugs used clinically indicate that the ideal agent has not been found. For example, mydriasis with photophobia and blurred vision occurs in most instances with clinical use of topical epinephrine. Consequently, this agent is contraindicated clinically in patients with narrow angle glaucoma due to the mydriasis and secondary blockage of aqueous outflow (1).
A program of pharmacological screening was instituted to detect a potential ocular hypotensive agent which might not demonstrate some of the undesirable side-effects exhibited by drugs of this class in current use clinically. The compound dl-1-(4-hydroxyphenyl)-2-isopropylaminoethanol hydrochloride (AL842) is one result of this testing program.
Initial studies undertaken to define the pharmacological properties of AL842 were performed in rabbits. The results of these experiments are reported elsewhere (2). In these studies the test methods utilized to determine ocular hypotensive activity depended upon an IOP which was initially increased artificially. In one system formalin was used to increase IOP secondarily to irritation and/ or inflammation (3). The second system was based on a modification of the water-provocative test used clinically in man (4). The nature of these tests, however, precluded the collection of onset-duration data.
A test system in animals was sought in which initial IOP was sufficiently high for potential ocular hypotensive properties to be demonstrated. Rhesus monkeys (Macaca mulatta) were chosen for these tests. Preliminary screening of IOP in these animals demonstrated an average IOP of approximately 16 mm Hg while approximately 13% of the animals recorded IOP values of 21 mm Hg or higher in at least one eye.
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