{"id":599,"date":"2026-02-25T12:19:22","date_gmt":"2026-02-25T11:19:22","guid":{"rendered":"https:\/\/5-ht7r.org\/?page_id=599"},"modified":"2026-02-25T12:19:22","modified_gmt":"2026-02-25T11:19:22","slug":"pharmacology","status":"publish","type":"page","link":"https:\/\/5-ht7r.org\/?page_id=599","title":{"rendered":"Pharmacology"},"content":{"rendered":"<style>\r\n\t.item {\r\n\t\tbackground-color:var(--global-color);\r\n\t\tcolor: white;\r\n    \tpadding: 14px 32px;\r\n    \tborder: none;\r\n    \tborder-radius: 25px;\r\n    \tfont-size: 1em;\r\n    \tcursor: pointer;\r\n    \ttransition: all 0.3s;\r\n    \tbox-shadow: 0 4px 15px rgba(0, 0, 0, 0.1);\r\n    \tfont-weight: 500;\t\t\r\n\t}\r\n\t.item:hover {\r\n\t\tbackground-color: lightblue;\r\n\t\tcolor: black;\r\n\t}\r\n\r\n<\/style>\r\n<div style=\"display:flex;flex-direction:row;justify-content:space-around\">\r\n\t<p class=\"item\" attrib=\"Agonists\" style=\"background:lightblue\">Agonists<\/p>\t\r\n    <p class=\"item\" attrib=\"Antagonists\" style=\"background:lightblue\">Antagonists<\/p>\t\r\n\t<p class=\"item\" attrib=\"Biasedligands\" style=\"background:lightblue\">Biased ligands<\/p>\t\r\n\t<p class=\"item\" attrib=\"Labelledligands\" style=\"background:lightblue\" >Labelled ligands<\/p>\r\n\t<p class=\"item\" attrib=\"Explorations\" style=\"background:lightblue\" >Explorations<\/p>\r\n<\/div>\r\n<div>\r\n\t<p class=\"paragraphe\" id=\"Agonists\" style=\"display:none\">\t\r\n\t\t to fill each topic\r\n\t<\/p>\r\n\t<p class=\"paragraphe\" id=\"Antagonists\" style=\"display:none\">\t\r\n\t\t to fill each topic\r\n\t<\/p>\r\n\t\r\n\t<p class=\"paragraphe\" id=\"Biasedligands\" style=\"display:block\">\t\r\n\t\tModulation of 5-HT<sub>7<\/sub>R activity has been the focus of numerous drug discovery and development programs <span class='tooltipsall tooltipsincontent classtoolTips0'>[14, 15]<\/span>. 5-HT<sub>7<\/sub>R is a member of the rhodopsin-like family of GPCRs, which counts more than 800 members in human making them a major class of drug targets: 40% of currently prescribed drug targets are GPCRs [16, 17]. However, identification of highly specific ligand is not a trivial task since GPCRs share a common 3D structure (heptahelical transmembrane domains). Though several 5-HT<sub>7<\/sub>R antagonists have been successfully developed during the past two decades, tested agonists often suffer from lack of specificity or a poor ability to cross the blood brain barrier (BBB). These are poor characteristics for a potential drug to be developed for central nervous system targets. To date, there are no approved medications targeted specifically to 5-HT7R. However, compounds with interesting pharmacokinetic properties have recently been developed as pain killers in different preclinical models [18, 19]. <br\/><br\/>\r\n\r\n\t\tDefined by McKinnon in 2001 <span class='tooltipsall tooltipsincontent classtoolTips8'>[20]<\/span> and <span class='tooltipsall tooltipsincontent classtoolTips2'>IUPHAR<\/span> [21], <b>biased signalling<\/b> has emerged as a new paradigm in <span class='tooltipsall tooltipsincontent classtoolTips5'>GPCR<\/span> pharmacology. Biased ligands are molecules which stabilize subsets of receptor conformations that exhibit a unique spectrum of pharmacological responses by specifically targeting G protein or \uf062-arrestin signalling [22]. Because they selectively modulate a subset of receptor functions, biased ligands may optimize therapeutic action and generate less pronounced side effects than compounds globally affecting receptor activity [23]. The duration of the drug-target complex, or residence time, seems to be a key determinant in their action mechanism and should be taken into consideration in modern drug discovery [24]. <br\/><br\/>\r\n\r\n\t\tThe host team has recently identified a 5-HT<sub>7<\/sub>R biased ligand, named Serodolin. Detailed pharmacological characterization of Serodolin revealed that it displays unexpected properties. Serodolin acts as a potent antagonist on the Gs coupled\/cAMP pathway (EC50 = 5 nM) but as an agonist on the ERK pathway. We demonstrated that this last effect is not mediated through G proteins but engages \u03b2\u2212arrestin-2 recruitment [18]. More interestingly, we validated that this unprecedented biased effect on 5-HT<sub>7<\/sub>R is not observed for other compounds utilized as 5-HT<sub>7<\/sub>R ligands, demonstrating that the pharmacological behaviour of the Serodolin chemical family was unique [18]. Work done by members of this proposed consortium support these findings. Studied in the cardiovascular system, serodolin was unable to cause vasorelaxation or a fall in blood pressure, but acted as a 5-HT<sub>7<\/sub>R antagonist [25]. This suggested that Gs but not \u03b2-arrestin biased agonists could be useful in reducing blood pressure. This new drug may be of interest to investigate the contribution of each pathway (Gs versus \u03b2\u2212arrestin) in physiological functions. <b>An open question that could be addressed by this consortium is: \u201cWhat are the promises and limitations of biased ligands of 5-HT<sub>7<\/sub>R?\u201d<\/b> \r\n\t<\/p> \r\n\t<p class=\"paragraphe\"  id=\"Labelledligands\" style=\"display:none\">\r\n\t\tto fill each topic\t\t\r\n\t<\/p>\r\n\t\r\n<\/div>\r\n\r\n<script>\r\n\tdocument.querySelectorAll(\".item\").forEach(elem=> {\r\n\t\telem.addEventListener(\"click\",function() {\r\n\t\t\tdocument.querySelectorAll(\".paragraphe\").forEach(Par=> Par.style.display=\"none\");\r\n\t\t\tdocument.querySelectorAll(\".item\").forEach(raz=>raz.style.background=\"#045cd8\");\r\n\t\t\tconst para = elem.getAttribute(\"attrib\");\r\n\t\t\tconsole.log(para);\r\n\t\t\tdocument.getElementById(para).style.display=\"block\";\r\n\t\t\tthis.style.background=\"lightblue\";\r\n\t\t});\r\n\t})\r\n\t\r\n<\/script><script type=\"text\/javascript\"> toolTips('.classtoolTips0','Blattner K M<em>, et al.<\/em>, Pharmacology and Therapeutic Potential of the 5-HT7 Receptor<em>.\u00a0<\/em>ACS Chem Neurosci,\u00a0<strong>2019<\/strong>. 10(1), 89-119,<br\/><br\/><strong>Deau E<\/strong><strong><em>, et al.<\/em><\/strong><strong>, Rational Design, Pharmacomodulation, and Synthesis of Dual 5-Hydroxytryptamine 7 (5-HT7)\/5-Hydroxytryptamine 2A (5-HT2A) Receptor Antagonists and Evaluation by [(18)F]-PET Imaging in a Primate Brain<\/strong><strong><em>.\u00a0<\/em><\/strong><strong>J Med Chem, 2015. 58(20), 8066-8096,<\/strong>'); <\/script><script type=\"text\/javascript\"> toolTips('.classtoolTips2','<a href=\"https:\/\/iuphar.org\/\"><img class=\"alignnone size-full wp-image-286\" src=\"https:\/\/5-ht7r.org\/wp-content\/uploads\/2026\/02\/IUPHAR-Logo-1.webp\" alt=\"\" width=\"150\" height=\"50\" \/><\/a>'); <\/script><script type=\"text\/javascript\"> toolTips('.classtoolTips5','<b>G protein-coupled receptors<\/b>'); <\/script><script type=\"text\/javascript\"> toolTips('.classtoolTips8','MacKinnon A C<em>, et al.<\/em>, Bombesin and substance P analogues differentially regulate G-protein coupling to the bombesin receptor. Direct evidence for biased agonism<em>.\u00a0<\/em>J Biol Chem,\u00a0<strong>2001<\/strong>. 276(30), 28083-28091'); <\/script>","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-599","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/pages\/599","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/5-ht7r.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=599"}],"version-history":[{"count":1,"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/pages\/599\/revisions"}],"predecessor-version":[{"id":600,"href":"https:\/\/5-ht7r.org\/index.php?rest_route=\/wp\/v2\/pages\/599\/revisions\/600"}],"wp:attachment":[{"href":"https:\/\/5-ht7r.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=599"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}