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Abstract #53559 Published in IGR 15-2

Melatonin and its analog 5-methoxycarbonylamino-N-acetyltryptamine potentiate adrenergic receptor-mediated ocular hypotensive effects in rabbits: significance for combination therapy in glaucoma

Crooke A; Huete-Toral F; Martínez-Águila A; Martín-Gil A; Pintor J
Journal of Pharmacology and Experimental Therapeutics 2013; 346: 138-145

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Melatonin is currently considered a promising drug for glaucoma treatment because of its ocular hypotensive and neuroprotective effects. We have investigated the effect of melatonin and its analog 5-methoxycarbonylamino-N-acetyltryptamine, 5-MCA-NAT, on β2/α2A-adrenergic receptor mRNA as well as protein expression in cultured rabbit nonpigmented ciliary epithelial cells. Quantitative polymerase chain reaction and immunocytochemical assays revealed a significant β2-adrenergic receptor downregulation as well as α2A-adrenergic receptor up-regulation of treated cells (P < 0.001, maximal significant effect). In addition, we have studied the effect of these drugs upon the ocular hypotensive action of a nonselective β-adrenergic receptor (timolol) and a selective α2-adrenergic receptor agonist (brimonidine) in normotensive rabbits. Intraocular pressure (IOP) experiments showed that the administration of timolol in rabbits pretreated with melatonin or 5-MCA-NAT evoked an additional IOP reduction of 14.02% ± 5.8% or 16.75% ± 5.48% (P < 0.01) in comparison with rabbits treated with timolol alone for 24 hours. Concerning brimonidine hypotensive action, an additional IOP reduction of 29.26% ± 5.21% or 39.07% ± 5.81% (P < 0.001) was observed in rabbits pretreated with melatonin or 5-MCA-NAT when compared with animals treated with brimonidine alone for 24 hours. Additionally, a sustained potentiating effect of a single dose of 5-MCA-NAT was seen in rabbits treated with brimonidine once daily for up 4 days (extra IOP decrease of 15.57% ± 5.15%, P < 0.05, compared with brimonidine alone). These data confirm the indirect action of melatoninergic compounds on adrenergic receptors and their remarkable effect upon the ocular hypotensive action mainly of α2-adrenergic receptor agonists but also of β-adrenergic antagonists.

Departamento de Bioquímica y Biología Molecular IV, Facultad de Óptica y Optometría, Universidad Complutense de Madrid, C/Arcos de Jalón 118, 28037 Madrid, Spain. jpintor@vet.ucm.es.

Full article

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Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
3.8 Pharmacology (Part of: 3 Laboratory methods)
5.3 Other (Part of: 5 Experimental glaucoma; animal models)

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