Purchase this article with an account.
Jesus J. Pintor, Antonio Bergua, Alejandro Martinez-Aguila; Topical Application of Anti-depressant Compound Agomelatine, a melatonin analogue, Reduces Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1967.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To investigate the possible hypotensive effect of the anti-depressant compound agomelatine, a melatonin analogue, in New Zealand rabbits
New Zealand white rabbits, weighting 3-4 Kg, were used for IOP studies. Agomelatine (Santa Cruz) was formulated in isotonic saline containing 1% DMSO (Sigma) and tested at different concentrations from 10-12 M to 10-4 M and was applied to the cornea at a fixed volume of 10 µL in the treated animals. The control animals received the same volume of saline + 1% DMSO. IOP was measured by means of a TonoVet® contact tonometer supplied by Tiolat Oy. Luzindole, Prazosin and 4PPDOT were used as antagonists of melatonin receptors.
Agomelatine applied at a concentration of 100 uM reduced IOP to 79.2 ±1.4 % compared to control (100 %). This maximal effect was obtained 180 min after the application of the compound (n=8). Concentration-response curve for this melatonin analogue presented a pD2 value of 9.7 ± 0.3, which was equivalent to an EC50 of 0.19 nM. Among the tested melatonin receptor antagonists, luzindole (MT1/MT2), 4-PPDOT (MT2) and Prazosin (MT3), the first did not modify the effect of agomelatine while the selective MT2 antagonist 4-PPDOT reduced IOP to 85.6 ± 1.6 % and Prazosin to 87.2 ± 1.9 % (n=18). The effect of agomelatine was compared to other commercial compounds such as Xalatan, Trusopt, Timolol and Alphagan, in this animal model. Among them only Trusopt and Timolol were more effective reducing IOP their values being 71.0 ± 2.0 % and 73.6 ± 1.8 % respectively.
Agomelatine present interesting properties reducing IOP. This is interesting since this compound belongs to melatonin analogues and not ot classical hypotensive drugs. The development of new melatonin compounds should expand the limited repertoire of drugs currently used for the treatment of glaucoma.
This PDF is available to Subscribers Only