Selective visualization of rat brain 5-HT2A receptors by autoradiography with [3H]MDL 100,907

The recently developed 5-HT_2A receptor selective antagonist ³H]MDL100,907 ((+/–)2,3-dimethoxyphenyl-1-2-(4-piperidine)-methanol]) has been characterized as a radioligand for the autoradiographic visualization of these receptors. ³H]MDL100,907 binding to rat brain tissue sections was saturable, had sub-nanomolar affinity (Kd=0.2–0.3nM), and presented a pharmacological profile consistent with its binding to 5-HT_2A receptors (rank order of affinity for ³H]MDL100,907-labelled receptors: MDL100,907 > spiperone > ketanserin > mesulergine). The distribution of receptors labelled by ³H]MDL100,907 was compared to the autoradiographical patterns obtained with ³H]Ketanserin, ³H]Mesulergine, and ³H]RP62203 (N-3-4-(4-fluorophenyl)-piperazin-1-y1]propyl]-1,8-naphtalenesultam) and to the distribution of 5-HT_2A receptor mRNA as determined by in situ hybridization. As opposed to the other radioligands, ³H]MDL100,907 labelled a single population of sites (5-HT_2A receptors) and presented extremely low levels of non-specific binding. The close similarity of the distributions of ³H]MDL100,907-labelled receptors and 5-HT_2A mRNA further supports the selectivity of this radioligand for 5-HT_2A receptors and suggests a predominant somatodendritic localization of these receptors. The present results point to ³H]MDL100,907 as the ligand of choice for the autoradiographic visualization of 5-HT_2A receptors. Received: 7 April / Accepted: 18 May 1997