Melatonin analogue agomelatine reduces rabbit's intraocular pressure in normotensive and hypertensive conditions

In the search for new compounds to reduce intraocular pressure (LOP), with fewer side effects, we have found that agomelatine, a melatonin analogue, can reduce LOP being, therefore, interesting for the treatment of ocular hypertension and glaucoma. In normotensive conditions, agomelatine (10 mu l 100 mu M) reduced LOP by 20.8 +/- 1.4% (n=18) with a maximal effect 180 min after the compound application and 68.8 +/- 5.7% (n=8) in a hypertensive condition. Concentration-response curve depicted a sigmoid behaviour presenting a pD2 value of 9.7 +/- 0.3 which was equivalent to an EC50 of 0.19 nM. The effect of agomelatine was partially antagonized by 4PPDOT (MT2 antagonist receptor. 10 mu l 100 mu M) and prazosin (MT3 antagonist receptor. 10 mu l 100 mu M) (85.6 +/- 1.6% and 87.2 +/- 1.9%, N=18 respectively.) Agomelatine hypotensive effect in normotensive condition was comparable to latanoprost (40 pi) and brimonidine (40 pi) and it was no so effective as dorzolamide (40 pi) or timolol (40 pi). These results may suggest the use of this melatonin analogue for the treatment of those ocular conditions, which involve an abnormal raise of intraocular pressure. (C) 2012 Elsevier BY. All rights reserved.