[3H]MDL 100,907 labels 5-HT2A serotonin receptors selectively in primate brain

Neuropharmacology. 1998 Sep;37(9):1147-58. doi: 10.1016/s0028-3908(98)00102-6.

Abstract

The selective antagonist for the 5-HT2A serotonin receptor MDL 100,907, 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]MDL 100,907 binding to brain sections was saturable, had sub-nanomolar affinity (Kd = 0.14-0.19 nM in human brain; Kd= 0.16-0.19 nM in monkey brain) and presented a pharmacological profile consistent with its binding to 5-HT2A receptors (rank order of affinity for [3H]MDL 100,907-labeled receptors: MDL 100,907 > spiperone > ketanserin > mesulergine). The autoradiographical signal obtained with [3H]MDL 100,907 was compared to the signal obtained with [3H]ketanserin, [3H]RP62203 and [3H]mesulergine in both species, and to the distribution of 5-HT2A receptor mRNA as determined by in situ hybridization in monkey brain. At variance with the other radioligands, [3H]MDL 100,907 showed a single population of binding sites with extremely low levels of non-specific binding. As expected, mesulergine showed low affinity for [3H]MDL 100,907-labeled receptors and the autoradiographic pattern shown by [3H]mesulergine confirmed the lack of labeling of the 5-HT2A receptor by this radioligand in primate brain. The similarity of the distribution of [3H]MDL 100,907-labeled receptors and 5-HT2A mRNA in monkey brain, supports the selectivity of this radioligand for 5-HT2A receptors and suggests a somatodendritic localization of these receptors. The present results confirm [3H]MDL 100,907 as the radioligand of choice at present for the autoradiographic visualization of 5-HT2A receptors in mammalian brain including post-mortem human brain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Binding Sites
  • Binding, Competitive
  • Brain / metabolism*
  • Cyclic S-Oxides / metabolism
  • Ergolines / metabolism
  • Female
  • Fluorobenzenes / metabolism*
  • Humans
  • In Situ Hybridization
  • Ketanserin / metabolism
  • Macaca fascicularis
  • Male
  • Naphthalenes / metabolism
  • Piperidines / metabolism*
  • RNA, Messenger / genetics
  • Radioligand Assay
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism*
  • Tritium

Substances

  • Cyclic S-Oxides
  • Ergolines
  • Fluorobenzenes
  • Naphthalenes
  • Piperidines
  • RNA, Messenger
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Tritium
  • fananserin
  • Ketanserin
  • volinanserin
  • mesulergine