WAY-100635

drugbox
ImageFile =
ImageSize =
IUPAC_name = "N"- [2- [4-(2-methoxyphenyl)-1-piperazinyl] ethyl] - "N"-(2-pyridyl)cyclohexanecarboxamide trihydrochloride
OtherNames =
CAS_number = 146714-97-8
PubChem=104911
SMILES=O=C(C1CCCCC1)N(CCN2CCN(c3ccccc3OC)CC2)c4ncccc4.Cl.Cl.Cl
C=25|H=37|Cl=3|N=4|O=2
molecular_weight = 531.94588

WAY-100635 is an organic compound that is a potent human dopamine receptor D4 full agonist, [Cite journal
author = Benjamin R. Chemel, Bryan L. Roth, Blaine Armbruster, Val J. Watts and David E. Nichols
title = WAY-100635 is a potent dopamine D4 receptor agonist
journal = Psychopharmacology
month = October
volume = 188
issue = 2
pages = 244–251.
year = 2006
pmid = 16915381
url = http://www.springerlink.com/content/vt36125287348028/
doi = 10.1007/s00213-006-0490-4] and a receptor antagonist for the serotonin-1A receptor. [Cite journal
author = C. A. Fornal, C. W. Metzler, R. A. Gallegos, S. C. Veasey, A. C. McCreary and B. L. Jacobs
title = WAY-100635, a potent and selective 5-hydroxytryptamine1A antagonist, increases serotonergic neuronal activity in behaving cats: comparison with (S)-WAY-100135
journal = The Journal of Pharmacology and Experimental Therapeutics
volume = 278
issue = 2
pages = 752–762
year = 1996
url = http://jpet.aspetjournals.org/cgi/content/abstract/278/2/752
pmid = 8768728] It is sometimes referred to as a silent antagonist for the latter receptor. [Cite journal
author = A. Fletcher, E. A. Forster, D. J. Bill, G. Brown, I. A. Cliffe, J. E. Hartley, D. E. Jones, A. McLenachan, K. J. Stanhope, D. J. Critchley, K. J. Childs, V. C. Middlefell, L. Lanfumey, R. Corradetti, A. M. Laporte, H. Gozlan, M. Hamon & C. T. Dourish
title = Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonist
journal = Behavioural Brain Research
volume = 73
issue = 1-2
pages = 337–333
year = 1996
month =
pmid = 8788530] Labeled with the radioisotope carbon-11 it is used as a radioligand in positron emission tomography (PET) studies of the serotonin-1A neuroreceptor in the brain. [Cite journal
author = Victor W. Pike, Julie A. McCarron, Adriaan A. Lammerstma, Susan P. Hume, Keith Poole, Paul M. Grasby, Andrea Malizia, Ian A. Cliffe, Allan Fletcher & Christopher J. Bench
title = First delineation of 5-HT_1A receptors in human brain with PET and [¹¹C] WAY-100635
journal = European Journal of Pharmacology
volume = 283
month = September
year = 1995
pages = R1–R3
doi = 10.1016/0014-2999(95)00438-Q
unused_data = |issues 1-3 ] WAY-100635 may be labeled in different ways with carbon-11: As [carbonyl-¹¹C] WAY-100635 or [O-methyl-¹¹C] WAY-100635, with [carbonyl-¹¹C] WAY-100635 regarded as "far superior". [Cite journal
author = Victor W. Pike, Julie A. McCarron, Adriaan A. Lammertsma, Safiye Osman, Susan P. Hume, Peter A. Sargent, Christopher J. Bench, Ian A. Cliffe, Alan Fletcher and Paul M. Grasby
title = Exquisite delineation of 5-HT_1A receptors in human brain with PET and [carbonyl-¹¹C] WAY-100635
journal = European Journal of Pharmacology
volume = 301
issues = 1-3
month = April
year = 1996
pages = R5–R7
doi = 10.1016/0014-2999(96)00079-9 ] Labeled with tritium WAY-100635 may also be used in autoradiography. [Cite journal
author = Susan P. Hume, Sharon Ashworth, Jolanta Opacka-Juffry, Randal G. Ahier, Adriaan A. Lammertsma, Victor W. Pike, Ian A. Cliffe, Allan Fletcher and Alan C. White
title = Evaluation of ["O-methyl"-³H] WAY-100635 as an in vivo radioligand for 5-HT_1A receptors in rat brain
journal = European Journal of Pharmacology
volume = 271
issues = 2-3
month = December
year = 1994
pages = 515–523
doi = 10.1016/0014-2999(94)90813-3] WAY-100635 has higher selectivity and 5-HT1A affinity than 8-OH-DPAT. [Cite journal
author = P. W. J. Burnet, S. L. Eastwood & P. J. Harrison
title = [³H] WAY-100635 for 5-HT_1A receptor autoradiography in human brain: a comparison with [³H] 8-OH-DPAT and demonstration of increased binding in the frontal cortex in schizophrenia
journal = Neurochemistry International
year = 1997
month = June
volume = 30
issue = 6
pages = 565–574
pmid = 9152998
doi = 10.1016/S0197-0186(96)00124-6]

Human PET studies

In human PET studies WAY-100635 shows high binding in the cerebral cortex, hippocampus, raphe nucleus and amygdaloid nucleus, while lower in thalamus and basal ganglia. [Cite journal
author = Hiroshi Ito, Christer Halldin & Lars Farde
title = Localization of 5-HT_1A receptors in the living human brain using carbonyl-¹¹CWAY-100635: PET with anatomic standardization technique
journal = Journal of Nuclear Medicine
volume = 40
issue = 1
pages = 102–109
year = 1999
month = January
pmid = 9935065
url = http://jnm.snmjournals.org/cgi/content/abstract/40/1/102] One study described a case with relatively high binding in the cerebellum. [Cite journal
author = Jussi Hirvonen, Jaana Kajander, Topias Allonen, Vesa Oikonen, Kjell Nagren & Jarmo Hietala
title = Measurement of serotonin 5-HT1A receptor binding using positron emission tomography and "carbonyl"-¹¹CWAY-100635—considerations on the validity of cerebellum as a reference region
journal = Journal of Cerebral Blood Flow and Metabolism
volume = 27
issue = 1
pages = 185–185
year = 2007
month = January
doi = 10.1038/sj.jcbfm.9600326
pmid = 16685258]

In relating its binding to subject variables one Swedish study found WAY-100635 binding in raphe brain region correlating with self-transcendence and spiritual acceptance personality traits.Cite journal
author = Jacqueline Borg, Bengt Andrée, Henrik Soderstrom, Lars Farde
title = The Serotonin System and Spiritual Experiences
journal = American Journal of Psychiatry
volume = 160
issue = 11
month = November
year = 2003
pages = 1965–1969
url = http://ajp.psychiatryonline.org/cgi/content/full/160/11/1965
doi = 10.1176/appi.ajp.160.11.1965] WAY-100635 binding has also been assessed in connection with clinical depression, where there has been disagreement about the presence and direction of the 5-HT_1A receptor binding. [Cite journal
author = Wayne C. Drevets, Michael E. Thase, Eydie L. Moses-Kolko, Julie Price, Ellen Frank, David J. Kupfer and Chester Mathis
title = Serotonin-1A receptor imaging in recurrent depression: replication and literature review
journal = Nuclear Medicin and Biology
year = 2007
month = October
volume = 34
issue = 7
pages = 865–877
pmid = 17921037
doi = 10.1016/j.nucmedbio.2007.06.008 ] In healthy subjects WAY-100635 binding has been found to decline with age,Cite journal
author = Johannes Tauscher, N. Paul L. G. Verhoeff, Bruce K. Christensen, Doug Hussey, Jeffrey H. Meyer, Alex Kecojevic, Mahan Javanmard, Siegfried Kasper and Shitij Kapur
title = Serotonin 5-HT_1A Receptor Binding Potential Declines with Age as Measured by [¹¹C] WAY-100635 and PET
journal = Neuropsychopharmacology
volume = 24
issue = 5
month = May
year = 2001
pages = 522–530
doi = 10.1016/S0893-133X(00)00227-X] — though not all studies have found this relationship.Cite journal
author = Rabiner EA, Messa C, Sargent PA, Husted-Kjaer K, Montgomery A, Lawrence AD, Bench CJ, Gunn RN, Cowen P, Grasby PM.
title = A database of [¹¹C] WAY-100635 binding to 5-HT_1A receptors in normal male volunteers: normative data and relationship to methodological, demographic, physiological, and behavioral variables
journal = NeuroImage
year = 2002
month = March
volume = 15
issue = 3
pages = 620–632
pmid = 11848705
doi = 10.1006/nimg.2001.0984 ] Cite journal
author = R. V. Parsey, M. A. Oquendo, N. R. Simpson, R. T. Ogden, R. Van Heertum, V. Arango V, J. J. Mann
title = Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT1A receptor binding potential measured by PET using [C-11] WAY-100635
journal = Brain Research
year = 2002
month = November
volume = 954
issue = 2
pages = 173–182
pmid = 12414100
doi = 10.1016/S0006-8993(02)03243-2]

See also

* Binding potential
* Other ligands for the serotonin system:
** Altanserin
** DASB

External links

* Cite web
url = http://www.turkupetcentre.net/analysis/doc/tracer/way100635.html
title = Quantification of (carbonyl-¹¹C)WAY-100635 PET studies
author = Vesa Oikonen
publisher = Turku PET center
year = 2007

References