Selective ligands as tools to study histamine receptors

In this review the histaminergic ligands for the histamine H-1, H-2 and H-3 receptors, which are currently used as tools in pharmacological studies, are described. To study interactions with the histamine H-1, receptor, the H-1 agonist 2-aminoethylthiazole has long since been used. However, during the last decade. 2-phenylhistamine derivatives emerged with interesting binding features. So far no radiolabelled selective H-1 agonist has been commonly used. As H-1 antagonists mepyramine, triprolidine and chlorpheniramine are described together with radiolabelled H-1 antagonists [H-3]mepyramine and [H-3]doxepin. Special attention has been paid to the PET ligands [C-11]doxepin and [C-11]mepyramine and the [I-125] labelled antagonists [I-125]iodobolpyramine and [I-125]iodoazidophenpyramine. Concerning H-2 agonists, especially dimaprit, amthamine and impromidine are discussed. There are several H-2 antagonists; amongst them cimetidine, tiotidine and ranitidine are used most frequently. Many of these antagonists behave as inverse agonists. As radiolabelled H-2 antagonists, [H-3]cimetidine, [H-3]tiotidine, [I-125]iodoaminopotentidine and [I-125]iodoazidopotentidine are included. Commonly used histamine H-3 agonists are N-alpha-methylhistamine, (R)alpha-methylhistamine, imetit and immepip. Both methylhistamines are also available as [H-3] labelled ligands. As reference compounds, often used H-3 antagonists are thioperamide; clobenpropit, iodophenpropit and impentamine. Most important radiolabelled H-3 antagonists are S-[H-3]methylthioperamide, [H-3]thioperamide, [I-125]iodophenpropit and [I-125]iodoproxyfan. The use of all these compounds as a tool in pharmacology is also discussed. (C) 2000 Editions scientifiques et medicales Elsevier SAS.