La Química médica en el desarrollo de las Sociedades. Biodiversidad y Productos naturales

This document has been prepared by the IUPAC Medicinal Chemistry section and is backed by a large number of scientists, many of whom have had direct involve-ment and whose names appear at the end of the article. This work discusses the role that the discovery of new medicinal agents has in the development of societies as well as in the conservation of biodiversity in terms of the work carried out on natural products. Also included are several recommendations for countries which are presently in search of their own scientific and technological development in medicinal agents. The IUPAC Medicinal Chemistry section would appreciate the collaboration of the scientific societies in every country to aid in the diffusion of this document.Se presenta un documento de opinión elaborado por la sección de Medicinal Chemistry de IUPAC, que cuenta además con el acuerdo de un buen número de científi-cos, algunos de los cuales figuran al final del trabajo. Se plantea el papel que puede tener el descubrimiento de medicamentos en el desarrollo de las sociedades y mantenimiento de la biodiversidad en base a los trabajos en productos naturales. Se plantean recomendaciones de aplicación en los países que están en la bús-queda de su desarrollo científico y tecnológico en el medicamento. Es intención de la sección de Medicinal Chemistry de IUPAC su difusión inter-nacional, por lo que agradecen la colaboración de las sociedades científicas de los dife-rentes países

Constitutive activity of the recombinant and native histamine H3 receptor

International audienceAlthough constitutive activity was shown to occur with many recombinant and/or mutated G-protein-coupled receptors, the physiological relevance of the process has remained debated. We have further explored this important issue with the histamine H3 receptor (H3R), a presynaptic receptor regulating histamine neuron activity in the brain. Constitutive activity of the recombinant receptor was studied using [3H]arachidonic acid release, [35S]GTPγ[S] binding and inhibition of cAMP accumulation. Evidence for constructive activity was obtained in these three functional assays with two isoforms of the rat H3 receptor, as well as with the human H3 receptor, expressed at physiological densities. Several standard H3-receptor antagonists, such as thioperamide and ciproxifan, were in fact acting as potent inverse agonists. Proxyfan opposed both agonists and inverse agonists and was therefore identified as a neutral antagonist. Using these drugs, we show high constitutive activity of native receptors. [35S]GTPγ[S] binding demonstrated constitutive activity of H3 receptors expressed at a normal level in mouse or rat brain. Constitutive activity of presynaptic H3 autoreceptors modulates histamine release from cortical synaptosomes in vitro and controls histamine neuron activity in vivo. This implies that inverse agonists rather than neutral antagonists may find therapeutic applications

S.16.04 Histamine H3-receptor ligands: Effects of inverse agonists and protean ligands

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