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T.J. Bunch, B.T. Gabelt, J.A. Kiland, E.A. Hennes, P.L. Kaufman; IOP Response to Topcial Noladin Ether in Cynomolgus Monkeys . Invest. Ophthalmol. Vis. Sci. 2006;47(13):216.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the effects of the cannabinoid (CB) agonist noladin ether (NE) and the CB1 antagonist AM 251, on intraocular pressure (IOP) in ocular normotensive cynomolgus monkeys.
Eight cynomolgus monkeys were studied. On baseline day and after 1 and 9 doses of b.i.d. topical treatments, the following measurements were made under ketamine sedation: IOP (minified Goldmann applanation tonometer) at 0, 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hours; slit lamp exams (SLE) at 0, 3, and 6 hours; refraction (Hartinger) and pupil diameter (calipers) at 0, 1, 3, and 6 hours. Treatments consisted of 62.5µg or 125µg NE (5x5µl) to one eye, vehicle to the opposite eye. Vehicle was initially 10% DMSO/40.5% hydroxypropyl–ß–cyclodextrin (HPßCD) but, due to solubility issues for other cannabinoid compounds being studied, 10% Tocrisolve/saline was subsequently used. The IOP response to the two vehicles, as well as the response to 125µg NE dissolved in each vehicle, were also compared. The IOP response to 125µg NE was determined following pretreatment with the CB1 antagonist, AM 251. One eye was treated with 25µg AM 251 (5x5µl); the opposite eye received Tocrisolve vehicle. Fifteen minutes later both eyes received 125µg NE (5x5µl). IOP and SLE data were collected after the 7th dose of b.i.d. treatments, as described above.
NE dose–dependently decreased IOP compared to the opposite eye and corrected for the baseline day IOP, with a greater efficacy after multiple treatments. The 62.5µg dose significantly (p<0.05) decreased IOP by approximately 2mmHg from hrs 1–6 after the 9th treatment. Prior to and after the 9th dose of 125µg NE, IOP was significantly decreased by 3–4 mmHg at all time points. SLE, refraction, and pupil diameter were not significantly affected. There was no difference in IOP response comparing the DMSO/HPßCD and Tocrisolve/saline vehicles alone or the IOP response after the 7th dose of 125µg NE formulated in either vehicle. The eyes that received AM 251 prior to NE treatment did not show significant changes in IOP from baseline; however the IOP of vehicle treated eyes was significantly decreased from baseline 1–2 hrs after treatment.
NE decreases IOP dose–dependently with no effect on SLE, refraction, or pupil diameter. There was no differential effect on IOP of the two different vehicles alone or when used to deliver NE topically. AM 251 appears to minimize the effects of NE, however additional experiments are required to determine whether the response is due to CB1 stimulation.
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