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J. J. Pintor, M. P. Alarma-Estrany, A. Peral, V. Andres, I. T. Molina-Martinez, R. Herrero-Vanrell; Enhanced Solubility of Melatonin Analogue 5-MCA-NAT, an Agonist of MT3 Receptors Reducing IOP. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3934.
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To solubilise the melatonin analogue 5-methoxyamino N-acetyltryptamine (5-MCA-NAT) which decreases IOP and may be used therefore for the treatment of glaucoma. Until date it has been dissolved in organic solvents such as DMSO and ethanol, not approved by FDA and EMEA.
All formulations including 5-MCA-NAT (100 µM and 500µM) were prepared by first solubilisation in PG. Then, aliquots were prepared with different vehicles containing variable proportions of PG:PBS (10:90, 25:75, and 50:50). Also 5-MCA-NAT was prepared in SystaneTM and isotonic PBS. As a control 5-MCA-NAT was also dissolved in DMSO. 10 µL of any of the vehicles containing 5-MCA-NAT dissolved in the corresponding composition were applied in New Zealand rabbit eyes. Contralateral eyes received the same volume of saline. IOP was measured by means of a TONOPEN® XL twice before the application of any solution and after that once every hour for at least 8 hours.
100 µM 5-MCA-NAT prepared in DMSO produced a reduction in IOP which was about 35 % compared to contralateral eyes. PG:PBS 10:90 reduced IOP 22.5 %, 25:75 reduced IOP 30 % and the ratio 50:50 reduced IOP 22 %. Highest proportions of propylenglycol produced discomfort plus ocular irritation and therefore were not taken for the present studies. SystaneTM reduced IOP 15 % while isotonic PBS reduced IOP 28 %. Concerning mean time effect, PG:PBS 10:90 and 50:50 produced effect which last longer than 3.5 hours while the ratio 25:75 lasted for about 7 hours.
The problems related to the solubility of 5-MCA-NAT have been overcome by means of a combination of propylenglycol and PBS, approaching these compounds to its use in clinical trials.
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