[3H]MDL 100,907 labels 5-HT2A serotonin receptors selectively in primate brain.
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.
López-Giménez
J F
JF
Department of Neurochemistry, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, Spain.
Vilaró
M T
MT
Palacios
J M
JM
Mengod
G
G
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D003499:Cyclic S-Oxides / Q000378:metabolism; D004873:Ergolines / Q000378:metabolism; D005260:Female; D005464:Fluorobenzenes / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D007650:Ketanserin / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D009281:Naphthalenes / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011869:Radioligand Assay; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D014316:Tritium
D003499:Cyclic S-Oxides; D004873:Ergolines; D005464:Fluorobenzenes; D009281:Naphthalenes; D010880:Piperidines; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D014316:Tritium; C070475:fananserin; D007650:Ketanserin; C079049:volinanserin; C031649:mesulergine