Molecular and cellular pharmacological properties of 5‐methoxycarbonylamino‐N‐acetyltryptamine (MCA‐NAT): a nonspecific MT3 ligand |
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Authors: | Ludwig Vincent William Cohen Philippe Delagrange Jean A Boutin Olivier Nosjean |
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Institution: | 1. Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, Croissy‐sur‐Seine, France;2. Département des Sciences Expérimentales, Institut de Recherches Servier, Suresnes, France |
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Abstract: | Abstract: 5‐Methoxycarbonylamino‐N‐acetyltryptamine (MCA‐NAT) has been initially described as a ligand at non MT1, non MT2 melatonin binding site (MT3) selective versus MT1 and MT2, two membrane melatonin receptors. MCA‐NAT activity has been reported by others in different models, in vivo, particularly in the intra‐ocular pressure (IOP) models in rabbits and monkeys. Its activity was systematically linked to either MT3 or to a new, yet unknown, melatonin receptor. In this article, the melatonin receptor pharmacology of MCA‐NAT is described. MCA‐NAT has micromolar range affinities at the melatonin receptors MT1 and MT2, while in functional studies, MCA‐NAT proved to be a powerful MT1/MT2 partial agonist in the sub‐micromolar range. These data strongly suggest that MCA‐NAT actions might be mediated by these receptors in vivo. Finally, as described by others, we show that MCA‐NAT is unable to elicit any type of receptor‐like functional responses from Chinese hamster ovary cells over‐expressing quinone reductase 2, the MT3. |
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Keywords: | 5‐Methoxycarbonylamino‐N‐acetyltryptamine melatonin receptors melatonin molecular pharmacology non MT1 non MT2 melatonin binding site |
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