DETERMINATION OF TOLERANCE TO TEAR PROTEIN RELEASE FOLLOWING A TWICE A DAY TOPICAL APPLICATION OF N,N-DIMETHYL-2-PHENYLETHYLAMINE HCL

In an effort to develop a long-term topically active tear stimulant, i t was important to determine if tolerance developed following the repe ated instillation of N,N-Dimethyl-2-phenylethylamine hydrochloride (AF 2975) to the albino rabbit eye. New Zealand white rabbits were adminis tered AF2975 (0.15 %) twice a day (9 am and 4:30 pm) for 10 days. The right eye received the drug solution (50 mu l) and the left eye receiv ed an equal volume of the vehicle. Prior to dosing and at the end of f irst and last dose (10 and 60 minutes post-dosing), protein secretion was measured with the use of Schirmer tear test strips placed under th e lower lid of each eye for five minutes. The strips absorbed tears fr om which protein was extracted. Eyes treated with AF2975 showed a stat istically significant % increase in protein release compared to baseli ne values. Control eyes did not show statistically significant increas es over baseline. A comparison of % changes from baseline in protein s ecretion rates after the first and last dose showed no significant dif ferences in either treated or control eyes at 10 and 60 minutes postdo sing. These results indicate that tolerance does not occur for protein secretion of topically administered AF2975 (0.15 %) following a twice a day dosing schedule for 10 days to the rabbit eye.