title: Melatonin analogue agomelatine reduces rabbit's intraocular pressure in normotensive and hypertensive conditions.
abstract: In the search for new compounds to reduce intraocular pressure (IOP), with fewer side effects, we have found that agomelatine, a melatonin analogue, can reduce IOP being, therefore, interesting for the treatment of ocular hypertension and glaucoma. In normotensive conditions, agomelatine (10μl 100μM) reduced IOP by 20.8±1.4% (n=18) with a maximal effect 180min 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 0.19nM. The effect of agomelatine was partially antagonized by 4PPDOT (MT2 antagonist receptor. 10μl 100μM) and prazosin (MT3 antagonist receptor. 10μl 100μM) (85.6±1.6% and 87.2±1.9%, N=18 respectively.) Agomelatine hypotensive effect in normotensive condition was comparable to latanoprost (40μl) and brimonidine (40μl) and it was no so effective as dorzolamide (40μl) or timolol (40μl). 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.
authors.affiliation: Dpto de Bioquímica y Biología Molecular IV, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martínez-Águila
authors.forename: Begoña
authors.initials: B
authors.lastname: Fonseca
authors.forename: Antonio
authors.initials: A
authors.lastname: Bergua
authors.forename: Jesús
authors.initials: J
authors.lastname: Pintor
mesh_terms: D000081:Acetamides / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007429:Intraocular Pressure / Q000187:drug effects*; D008550:Melatonin / Q000031:analogs & derivatives*; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D011817:Rabbits; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D008550:Melatonin; C084711:agomelatine; D009281:Naphthalenes