Page 139 - 73_04

VOL. 73 (4), 947-962, 2007 MELATONIN MAKES ME FEEL AWAKE!...

the studies regarding nucleotides and dinucleotides as modulators of
IOP I wanted to finish.

FIGURE 1. Comparison between the concentration of melatonin and the
changes in IOP along day and night.

This delay was positive since in the months that passed from the
moment I did the experiments with melatonin to the one I started to
continue it, January 2000, a paper appeared describing some new
compounds which selectively activate the three different subtypes of
melatonin receptors, MT1, MT2 and MT3 (2) (Figure 2). Basically my
idea was to repeat that melatonin experiment and then to assay
different agonists and antagonists of the melatonin receptors in order
to pharmacologically characterise the receptor reducing IOP in
rabbits.

So, after getting a positive hypotensive effect with melatonin, the
next decision was to choose which one was going to be the following
compound to be assayed. At that moment I had bought a battery of
compounds so it was at the beginning a bit difficult to decide how
to start. I thought that assaying the newest compounds would
provide an attractive starting point if, of course, they work. The
newest substance was 5-methoxyamino N-acetyltryptamine (5-MCA-
NAT) and this was the first I assayed. When the experiments were
performed with this compound the results were amazing: IOP was
reduced almost 40 % and the duration of the effect was longer than
8 hours, just with a single dose of 100 µM 5-MCA-NAT. Compared
to melatonin, this agonist was much better than the naturally
occurring substance (Figure 3). Moreover, 5-MCA-NAT was a
selective melatonin MT3 receptor (3).

949