title: Effect of Melatonin and 5-Methoxycarbonylamino-N-Acetyltryptamine on the Intraocular Pressure of Normal and Glaucomatous Mice.
abstract: Melatonin is a neurohormone that is produced not only by the pineal gland but also by several ocular structures. One of the main physiologic roles of melatonin is the reduction of intraocular pressure (IOP). Using both control C57BL/6J and glaucomatous DBA/2J mice as well as TonoLab tonometry, this study evaluated the effect of melatonin and 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) when glaucomatous pathology was fully established and compared pharmacological behavior in treated mice versus control mice. In addition, 5-MCA-NAT was tested to determine its effects on ameliorating increased IOP in a glaucoma model. The results demonstrate that melatonin and 5-MCA-NAT can reduce IOP in a concentration-dependent manner. The EC50values for melatonin in control and glaucomatous animals were 34µM and 50µM, respectively. Interestingly, melatonin decreased IOP in 19.4% ± 3.7% and 32.6% ± 6.0% of control and glaucomatous mice, respectively, when the animals were studied at age 12 months. 5-MCA-NAT reduced IOP in the same manner and was able to stop IOP progression in glaucomatous mice. Use of melatonin receptor antagonists showed that hypotensive effects were blocked by the MT2receptor antagonists luzindole and 4-phenyl-2-propionamidotetralin in the case of melatonin and by only 4-phenyl-2-propionamidotetralin in the case of 5-MCA-NAT. In conclusion, melatonin and 5-MCA-NAT can effectively reduce IOP in a glaucoma model, and their hypotensive effects are more profound in the glaucoma model than in control animals.
authors.affiliation: Departmento de Bioquímica y Biología Molecular IV, Facultad de Óptica y Optometría, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Alejandro
authors.identifier: http://orcid.org/0000-0001-8228-8180
authors.initials: A
authors.lastname: Martínez-Águila
authors.affiliation: Departmento de Bioquímica y Biología Molecular IV, Facultad de Óptica y Optometría, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Fonseca
authors.affiliation: Departmento de Bioquímica y Biología Molecular IV, Facultad de Óptica y Optometría, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Pérez de Lara
authors.affiliation: Departmento de Bioquímica y Biología Molecular IV, Facultad de Óptica y Optometría, Universidad Complutense de Madrid, Madrid, Spain jpintor@vet.ucm.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pintor
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005901:Glaucoma / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D007429:Intraocular Pressure / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D044123:Receptor, Melatonin, MT2 / Q000037:antagonists & inhibitors; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: C114459:4-phenyl-2-propionamidotetraline; C413586:5-methoxycarbonylamino-N-acetyltryptamine; D044123:Receptor, Melatonin, MT2; D013764:Tetrahydronaphthalenes; D014363:Tryptamines; C057154:luzindole; D008550:Melatonin