[3H]MDL100,907 labels 5-HT(2A) serotonin receptors selectively in primate brain

Abstract

The selective antagonist for the 5-HT(2A) serotonin receptor MDL100,907, recently characterized autoradiographically in rat brain, has been characterized as a radioligand for the visualization of this receptor in human and monkey brain. In both species [3H]MDL100,907 binding to brain sections was saturable, had sub-nanomolar affinity (K(d)=0.14-0.19 nM in human brain; K(d)=0.16-0.19 nM in monkey brain) and presented a pharmacological profile consistent with its binding to 5-HT(2A) receptors (rank order of affinity for [3H]MDL100,907-labeled receptors: MDL100,907>spiperone>ketanserin>mesulergine). The autoradiographical signal obtained with [3H]MDL100,907 was compared to the signal obtained with [3H]ketanserin, [3H]RP62203 and [3H]mesulergine in both species, and to the distribution of 5-HT(2A) receptor mRNA as determined by in situ hybridization in monkey brain. At variance with the other radioligands, [3H]MDL100,907 showed a single population of binding sites with extremely low levels of non-specific binding. As expected, mesulergine showed low affinity for [3H]MDL100,907-labeled receptors and the autoradiographic pattern shown by [3H]mesulergine confirmed the lack of labeling of the 5-HT(2A) receptor by this radioligand in primate brain. The similarity of the distribution of [3H]MDL100,907-labeled receptors and 5-HT(2A) mRNA in monkey brain, supports the selectivity of this radioligand for 5-HT(2A) receptors and suggests a somatodendritic localization of these receptors. The present results confirm [3H]MDL100,907 as the radioligand of choice at present for the autoradiographic visualization of 5-HT(2A) receptors in mammalian brain including post-mortem human brain. Copyright (C) 1998 Elsevier Science Ltd.