A retrospect on the discovery of WAY-100635 and the prospect for improved 5-HT(1A) receptor PET radioligands.
Abstract. An outline is given of the developments that led to the identification of [O-methyl-(11)C]WAY-100635 (4) as the first useful PET ligand for imaging serotonin(1A) (5-HT(1A)) receptors in the living human brain. Recent attempts to develop 5-HT(1A) receptor radioligands superior to 4 are reviewed, and [carbonyl-(11)C]WAY-100635 (6) has been shown to be the best currently available radioligand for human studies. Of other (11)C-radiolabelled compounds, [O-methyl-(11)C](R,S)-CPC-222 (9), DWAY (8), and [(11)C]NAD-299 (14) all demonstrate specific binding to 5-HT(1A) receptors in animals and warrant further expedited studies in humans. The trans-fluorocyclohexane, 12, and fluorobenzene, [(18)F]p-MPPF 13, are highlighted as examples of promising (18)F-labelled ligands.
Cliffe
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Department of Chemistry, Vernalis Research, Oakdene Court, 613 Reading Road, Winnersh, Workingham RG41 5UA, United Kingdom. i.cliffe@vernalis.com
D000818:Animals; D002250:Carbon Radioisotopes; D006801:Humans; D008024:Ligands; D010879:Piperazines / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000032:analysis*; D044263:Receptors, Serotonin, 5-HT1; D012189:Retrospective Studies; D012702:Serotonin Antagonists / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D008024:Ligands; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide