WAY-100,635

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WAY-100,635
200px
Systematic (IUPAC) name
N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-(2-pyridyl)cyclohexanecarboxamide
Identifiers
CAS Number 146714-97-8
PubChem CID 5684
IUPHAR/BPS 80
Chemical data
Formula C25H34N4O2
Molar mass 422.56 g/mol[[Script error: No such module "String".]]
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WAY-100,635 is a piperazine drug and research chemical widely used in scientific studies. It was originally believed to act as a selective 5-HT1A receptor antagonist, but subsequent research showed that it also acts as potent full agonist at the D4 receptor.[1][2][3] It is sometimes referred to as a silent antagonist at the former receptor.[4] It is closely related to WAY-100,135.

In light of its only recently discovered dopaminergic activity, conclusions drawn from studies that employed WAY-100635 as a selective 5-HT1A antagonist may need to be re-evaluated.

Human PET studies

In human PET studies WAY-100,635 shows high binding in the cerebral cortex, hippocampus, raphe nucleus and amygdaloid nucleus, while lower in thalamus and basal ganglia.[5] One study described a case with relatively high binding in the cerebellum.[6]

In relating its binding to subject variables one Swedish study found WAY-100,635 binding in raphe brain region correlating with self-transcendence and spiritual acceptance personality traits.[7] WAY-100,635 binding has also been assessed in connection with clinical depression, where there has been disagreement about the presence and direction of the 5-HT1A receptor binding.[8] In healthy subjects WAY-100,635 binding has been found to decline with age,[9] — though not all studies have found this relationship.[10][11]

Human WAY-100635 binding neuroimaging studies (patients compared to healthy control subjects).
What Result Subjects Ref.
Age Global decrease and particularly in parietal cortex and dorsolateral prefrontal cortex 19 [9]
Age No correlation found 61 [10]
Age No correlation detected 25 [11]
Sex Higher binding in females 25 [11]
TCI self-transcendence and spiritual acceptance personality traits Positive correlation in raphe region 15 males [7]
Lifetime aggression Negative correlation 25 [11]
MADAM binding potential (serotonin transporter binding) Positive correlation in the raphe nuclei and hippocampus 12 males [12]
Genetic variation Result Subjects Ref.
HTR1A.(-1018)C>G polymorphism No difference found 35 [13]
SERT.5-HTTLPR polymorphism Lower binding in "all brain regions" for SS or SL genotypes compared to LL 35 [13]
Disease Result Subjects Ref.
Depressive (with primary, recurrent, familial mood disorders) Reduction in raphe nucleus and mesiotemporal cortex 12+8 [14]
Major depressive disorder (medicated and unmedicated) Reduction in "many of the regions examined" 25+18 [15]
Panic disorder in treated and untreated patients Reducing in binding in raphe in both treated and untreated. Reduced binding in global postsynaptic regions for untreated, while no or little reduction for treated. 9+7+19 [16]
Alzheimer disease Decrease in right medial temporal cortex 10+10 [17]

Radioligands

Labeled with the radioisotope carbon-11 it is used as a radioligand in positron emission tomography (PET) studies to determine neuroreceptor binding in the brain.[18] WAY-100,635 may be labeled in different ways with carbon-11: As [carbonyl-11C]WAY-100,635 or [O-methyl-11C]WAY-100,635, with [carbonyl-11C]WAY-100635 regarded as "far superior".[19] Labeled with tritium WAY-100,635 may also be used in autoradiography.[20] WAY-100,635 has higher 5-HT1A affinity than 8-OH-DPAT.[21]

See also

External links

References

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  1. ↑ C. A. Fornal, C. W. Metzler, R. A. Gallegos, S. C. Veasey, A. C. McCreary and B. L. Jacobs (1996). "WAY-100635, a potent and selective 5-hydroxytryptamine1A antagonist, increases serotonergic neuronal activity in behaving cats: comparison with (S)-WAY-100135". The Journal of Pharmacology and Experimental Therapeutics. 278 (2): 752–762. PMID 8768728. 
  2. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  3. ↑ Marona-Lewicka D, Nichols DE (2009). "WAY 100635 produces discriminative stimulus effects in rats mediated by dopamine D(4) receptor activation". Behav Pharmacol. 20 (1): 114–8. doi:10.1097/FBP.0b013e3283242f1a. PMID 19179855. 
  4. ↑ 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 (1996). "Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonist". Behavioural Brain Research. 73 (1-2): 337–333. doi:10.1016/0166-4328(96)00118-0. PMID 8788530. 
  5. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  6. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  7. ↑ 7.0 7.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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  10. ↑ 10.0 10.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  11. ↑ 11.0 11.1 11.2 11.3 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  12. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  13. ↑ 13.0 13.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  14. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  15. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  16. ↑ Jon R. Nash, Peter A. Sargent, Eugenii A. Rabiner, Sean D. Hood, Paul M. Grasby & David J. Nutt (2008). "Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study". The British Journal of Psychiatry. 193: 229–234. doi:10.1192/bjp.bp.107.041186. 
  17. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  18. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  19. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  20. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  21. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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