Summary
5-HT4 receptors have recently been discovered in brain (foetal mice neurons, adult guinea pig hippocampus) and also in guinea pig ileum and ascending colon, rat oesophagus, pig and human heart. These 5-HT4 receptors have been shown to stimulate cAMP production in brain and heart and to inhibit voltage-dependent K+ channels in colliculi neurons.
The pharmacological characteristics of 5-HT4 receptors are very particular. Indole derivatives, including 5 substituted tryptamine agonists, are generally active (especially 5-methoxytryptamine, 5-carboxamidotryptamine, RU 28253). All the 2-methoxy-4-amino-5-chloro substituted benzamide derivatives tested so far, are agonists as are the azabicycloalkylbenzimidazolone derivatives. Classical pharmacological criteria indicate that indole, benzamides and azabicycloalkylbenzimidazolone derivatives act on the same receptor molecule entity. However, [3H]-renzapride (benzamide) binding sites on colliculi membranes are not displaced by indole derivatives including 5-HT, 5-methoxytryptamine and RU 28253. This indicates that either [3H]-renzapride binding sites are unrelated to 5-HT4 receptors or that benzamides and indole derivatives interact at different subsites of the 5-HT4 receptor. The only 5-HT4 receptor antagonist described to date is ICS 205 930 (a competitive antagonist). The affinity of this drug is far lower (μM) than its affinity for 5-HT3 receptors (nM). Finally, another particularity of the 5-HT4 rceptor is its rapid desensitization.
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© 1991 Birkhäuser Verlag Basel/Switzerland
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Bockaert, J., Fagni, L., Sebben, M., Dumuis, A. (1991). Pharmacological Characterization of Brain 5-HT4 Receptors: Relationship between the Effects of Indole, Benzamide and Azabicycloalkybenzimidazolone Derivatives. In: Fozard, J.R., Saxena, P.R. (eds) Serotonin: Molecular Biology, Receptors and Functional Effects. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7259-1_20
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