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Abstract #9925 Published in IGR 5-3

Ocular hypotensive effects of melatonin receptor agonists in the rabbit: further evidence for an MT3 receptor

Pintor J; Pelaez T; Hoyle CH; Peral A
British Journal of Pharmacology 2003; 138: 831-836

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Melatonin is involved in the control of intraocular pressure (IOP) during the night and day photoperiod. The authors investigated the receptor that regulates IOP in New Zealand white rabbits by means of agonists and antagonists of melatonin receptors. Melatonin and its analogues: 2-Phe-melatonin, 6-Cl-melatonin, 2-I-melatonin, 5- methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) and N-acetyltryptamine all produced a reduction in IOP. Dose-response analysis for these compounds gave pD₂ values of 9.3 ± 0.24 for melatonin; 9.0 ± 0.09 for 6-Cl-melatonin; 9.0 ± 0.84 for 2-I-melatonin; 8.9 ± 0.07 for 5-MCA-NAT; 8.7 ± 0.18 for 2-Phe-melatonin, and 9.4 ± 0.30 for N-acetyltryptamine (all n = 8). At a dose of 0.5 nmol (in 10 μl) melatonin and the selective melatonin MT₃ agonist 5-MCA-NAT, induced greater reductions of IOP (22.8 ± 2.3% and 32.5 ± 1.4%, respectively) than the other compounds. The melatonin-receptor antagonists, prazosin, DH-97 and 4-P-PDOT, reversed the effect of 5-MCA-NAT in a dose-dependent manner, with pA₂ values of 13.5 ± 0.17 for prazosin, 10.6 ± 0.16 for DH-97 and 9.4 ± 0.20 for 4-P-PDOT (n = 8). Cholinoceptor antagonists (hexamethonium and atropine) and α₂- and β₂-adrenoceptor antagonists (yohimbine and ICI 118,551) partially reversed the effects produced by melatonin and 5-MCA-NAT, suggesting the possible involvement of cholinergic and noradrenergic systems in the hypotensive actions mediated by melatonin agonists. The α₁-adrenoceptor antagonist, corynanthine, had no significant effect. The strong hypotensive effect of the MT₃ agonist, 5-MCA-NAT, suggests that this compound may be a useful agent for treating those pathologies where IOP is abnormally elevated.

Dr. J. Pintor, Departamento de Bioquimica y Biologia Molecular IV, E.U. Optica, c/ Arcos de Jalon s/n, 28037 Madrid, Spain

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Classification:

11.4 Prostaglandins (Part of: 11 Medical treatment)

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