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Formula | C25H34N4O2 |
Molar mass | 422.573 g·mol−1 |
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WAY-100635 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-100135.
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.[5]
Human PET studies
[edit]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.[6] One study described a single case with relatively high binding in the cerebellum.[7]
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.[8] 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-HT1A receptor binding.[9] In healthy subjects WAY-100635 binding has been found to decline with age,[10] — though not all studies have found this relationship.[11][12]
What | Result | Subjects | Ref. |
---|---|---|---|
Age | Global decrease and particularly in parietal cortex and dorsolateral prefrontal cortex | 19 | [10] |
Age | No correlation found | 61 | [11] |
Age | No correlation detected | 25 | [12] |
Sex | Higher binding in females | 25 | [12] |
TCI self-transcendence and spiritual acceptance personality traits | Positive correlation in raphe region | 15 males | [8] |
Lifetime aggression | Negative correlation | 25 | [12] |
MADAM binding potential (serotonin transporter binding) | Positive correlation in the raphe nuclei and hippocampus | 12 males | [13] |
Genetic variation | Result | Subjects | Ref. |
HTR1A.(-1018)C>G polymorphism | No difference found | 35 | [14] |
SERT.5-HTTLPR polymorphism | Lower binding in "all brain regions" for SS or SL genotypes compared to LL | 35 | [14] |
Disease | Result | Subjects | Ref. |
Depressive (with primary, recurrent, familial mood disorders) | Reduction in raphe nucleus and mesiotemporal cortex | 12+8 | [15] |
Major depressive disorder (medicated and unmedicated) | Reduction in "many of the regions examined" | 25+18 | [16] |
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 | [17] |
Alzheimer disease | Decrease in right medial temporal cortex | 10+10 | [18] |
Radioligands
[edit]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.[19] 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".[20] Labeled with tritium WAY-100635 may also be used in autoradiography.[21] WAY-100635 has higher 5-HT1A affinity than 8-OH-DPAT.[22]
Other actions
[edit]WAY-100635 has also been found to increase the analgesic effects of opioid drugs in a dose-dependent manner, in contrast to 5-HT1A agonists such as 8-OH-DPAT which were found to reduce opioid analgesia.[23][24] However, since 5-HT1A agonists were also found to reduce opioid-induced respiratory depression and WAY-100635 was found to block this effect,[25] it is likely that 5-HT1A antagonists might worsen this side effect of opioids. Paradoxically, chronic administration of the very high efficacy 5-HT1A agonist befiradol results in potent analgesia following an initial period of hyperalgesia, an effect most likely linked to desensitisation and/or downregulation of 5-HT1A receptors (i.e. analogous to a 5-HT1A antagonist-like effect).[26][27][28] As with other 5-HT1A silent antagonists such as UH-301 and robalzotan, WAY-100635 can also induce a head-twitch response in rodents.[29]
See also
[edit]- Binding potential
- Other radioligands for the serotonin system:
External links
[edit]- Vesa Oikonen (2007). "Quantification of (carbonyl-11C)WAY-100635 PET studies". Turku PET center.
References
[edit]- ^ Fornal CA, Metzler CW, Gallegos RA, Veasey SC, McCreary AC, Jacobs BL (August 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.
- ^ Chemel BR, Roth BL, Armbruster B, Watts VJ, Nichols DE (October 2006). "WAY-100635 is a potent dopamine D4 receptor agonist". Psychopharmacology. 188 (2): 244–251. doi:10.1007/s00213-006-0490-4. PMID 16915381. S2CID 24194034.
- ^ Marona-Lewicka D, Nichols DE (February 2009). "WAY 100635 produces discriminative stimulus effects in rats mediated by dopamine D(4) receptor activation". Behavioural Pharmacology. 20 (1): 114–118. doi:10.1097/FBP.0b013e3283242f1a. PMID 19179855. S2CID 43332577.
- ^ Fletcher A, Forster EA, Bill DJ, Brown G, Cliffe IA, Hartley JE, et al. (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): 337–353. doi:10.1016/0166-4328(96)00118-0. PMID 8788530. S2CID 18229202.
- ^ Chemel BR, Roth BL, Armbruster B, Watts VJ, Nichols DE (October 2006). "WAY-100635 is a potent dopamine D4 receptor agonist". Psychopharmacology. 188 (2): 244–251. doi:10.1007/s00213-006-0490-4. PMID 16915381. S2CID 24194034.
- ^ Ito H, Halldin C, Farde L (January 1999). "Localization of 5-HT1A receptors in the living human brain using [carbonyl-11C]WAY-100635: PET with anatomic standardization technique". Journal of Nuclear Medicine. 40 (1): 102–109. PMID 9935065.
- ^ Hirvonen J, Kajander J, Allonen T, Oikonen V, Någren K, Hietala J (January 2007). "Measurement of serotonin 5-HT1A receptor binding using positron emission tomography and [carbonyl-(11)C]WAY-100635-considerations on the validity of cerebellum as a reference region". Journal of Cerebral Blood Flow and Metabolism. 27 (1): 185–195. doi:10.1038/sj.jcbfm.9600326. PMID 16685258.
- ^ a b Borg J, Andrée B, Soderstrom H, Farde L (November 2003). "The serotonin system and spiritual experiences". The American Journal of Psychiatry. 160 (11): 1965–1969. doi:10.1176/appi.ajp.160.11.1965. PMID 14594742. S2CID 5911066.
- ^ Drevets WC, Thase ME, Moses-Kolko EL, Price J, Frank E, Kupfer DJ, Mathis C (October 2007). "Serotonin-1A receptor imaging in recurrent depression: replication and literature review". Nuclear Medicine and Biology. 34 (7): 865–877. doi:10.1016/j.nucmedbio.2007.06.008. PMC 2702715. PMID 17921037.
- ^ a b Tauscher J, Verhoeff NP, Christensen BK, Hussey D, Meyer JH, Kecojevic A, et al. (May 2001). "Serotonin 5-HT1A receptor binding potential declines with age as measured by [11C]WAY-100635 and PET". Neuropsychopharmacology. 24 (5): 522–530. doi:10.1016/S0893-133X(00)00227-X. PMID 11282252.
- ^ a b Rabiner EA, Messa C, Sargent PA, Husted-Kjaer K, Montgomery A, Lawrence AD, et al. (March 2002). "A database of [(11)C]WAY-100635 binding to 5-HT(1A) receptors in normal male volunteers: normative data and relationship to methodological, demographic, physiological, and behavioral variables". NeuroImage. 15 (3): 620–632. doi:10.1006/nimg.2001.0984. PMID 11848705. S2CID 42080193.
- ^ a b c d Parsey RV, Oquendo MA, Simpson NR, Ogden RT, Van Heertum R, Arango V, Mann JJ (November 2002). "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". Brain Research. 954 (2): 173–182. doi:10.1016/S0006-8993(02)03243-2. PMID 12414100. S2CID 20650203.
- ^ Lundberg J, Borg J, Halldin C, Farde L (December 2007). "A PET study on regional coexpression of 5-HT1A receptors and 5-HTT in the human brain". Psychopharmacology. 195 (3): 425–433. doi:10.1007/s00213-007-0928-3. PMID 17874074. S2CID 22272672.
- ^ a b David SP, Murthy NV, Rabiner EA, Munafó MR, Johnstone EC, Jacob R, et al. (March 2005). "A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans". The Journal of Neuroscience. 25 (10): 2586–2590. doi:10.1523/JNEUROSCI.3769-04.2005. PMC 1942077. PMID 15758168.
- ^ Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, et al. (November 1999). "PET imaging of serotonin 1A receptor binding in depression". Biological Psychiatry. 46 (10): 1375–1387. doi:10.1016/S0006-3223(99)00189-4. PMID 10578452. S2CID 719822.
- ^ Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, et al. (February 2000). "Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment". Archives of General Psychiatry. 57 (2): 174–180. doi:10.1001/archpsyc.57.2.174. PMID 10665620.
- ^ Nash JR, Sargent PA, Rabiner EA, Hood SD, Argyropoulos SV, Potokar JP, et al. (September 2008). "Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study". The British Journal of Psychiatry. 193 (3): 229–234. doi:10.1192/bjp.bp.107.041186. PMID 18757983.
- ^ Lanctôt KL, Hussey DF, Herrmann N, Black SE, Rusjan PM, Wilson AA, et al. (October 2007). "A positron emission tomography study of 5-hydroxytryptamine-1A receptors in Alzheimer disease". The American Journal of Geriatric Psychiatry. 15 (10): 888–898. doi:10.1097/JGP.0b013e3180488325. PMID 17567932.
- ^ Pike VW, McCarron JA, Lammerstma AA, Hume SP, Poole K, Grasby PM, et al. (September 1995). "First delineation of 5-HT1A receptors in human brain with PET and [11C]WAY-100635". European Journal of Pharmacology. 283 (1–3): R1–R3. doi:10.1016/0014-2999(95)00438-Q. PMID 7498295.
- ^ Pike VW, McCarron JA, Lammertsma AA, Osman S, Hume SP, Sargent PA, et al. (April 1996). "Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11 C]WAY-100635". European Journal of Pharmacology. 301 (1–3): R5–R7. doi:10.1016/0014-2999(96)00079-9. PMID 8773468.
- ^ Hume SP, Ashworth S, Opacka-Juffry J, Ahier RG, Lammertsma AA, Pike VW, et al. (December 1994). "Evaluation of [O-methyl-3H]WAY-100635 as an in vivo radioligand for 5-HT1A receptors in rat brain". European Journal of Pharmacology. 271 (2–3): 515–523. doi:10.1016/0014-2999(94)90813-3. PMID 7705452.
- ^ Burnet PW, Eastwood SL, Harrison PJ (June 1997). "[3H]WAY-100635 for 5-HT1A receptor autoradiography in human brain: a comparison with [3H]8-OH-DPAT and demonstration of increased binding in the frontal cortex in schizophrenia". Neurochemistry International. 30 (6): 565–574. doi:10.1016/S0197-0186(96)00124-6. PMID 9152998. S2CID 21135585.
- ^ Bardin L, Colpaert FC (June 2004). "Role of spinal 5-HT(1A) receptors in morphine analgesia and tolerance in rats". European Journal of Pain. 8 (3): 253–261. doi:10.1016/j.ejpain.2003.09.002. PMID 15109976. S2CID 25580572.
- ^ Berrocoso E, De Benito MD, Mico JA (July 2007). "Role of serotonin 5-HT1A and opioid receptors in the antiallodynic effect of tramadol in the chronic constriction injury model of neuropathic pain in rats". Psychopharmacology. 193 (1): 97–105. doi:10.1007/s00213-007-0761-8. PMID 17393145. S2CID 21898521.
- ^ Sahibzada N, Ferreira M, Wasserman AM, Taveira-DaSilva AM, Gillis RA (February 2000). "Reversal of morphine-induced apnea in the anesthetized rat by drugs that activate 5-hydroxytryptamine(1A) receptors". The Journal of Pharmacology and Experimental Therapeutics. 292 (2): 704–713. PMID 10640309.
- ^ Bardin L, Assié MB, Pélissou M, Royer-Urios I, Newman-Tancredi A, Ribet JP, et al. (March 2005). "Dual, hyperalgesic, and analgesic effects of the high-efficacy 5-hydroxytryptamine 1A (5-HT1A) agonist F 13640 [(3-chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl}piperidin-1-yl]methanone, fumaric acid salt]: relationship with 5-HT1A receptor occupancy and kinetic parameters". The Journal of Pharmacology and Experimental Therapeutics. 312 (3): 1034–1042. doi:10.1124/jpet.104.077669. PMID 15528450. S2CID 42446435.
- ^ Assié MB, Lomenech H, Ravailhe V, Faucillon V, Newman-Tancredi A (September 2006). "Rapid desensitization of somatodendritic 5-HT1A receptors by chronic administration of the high-efficacy 5-HT1A agonist, F13714: a microdialysis study in the rat". British Journal of Pharmacology. 149 (2): 170–178. doi:10.1038/sj.bjp.0706859. PMC 2013794. PMID 16921393.
- ^ Buritova J, Berrichon G, Cathala C, Colpaert F, Cussac D (February 2009). "Region-specific changes in 5-HT1A agonist-induced Extracellular signal-Regulated Kinases 1/2 phosphorylation in rat brain: a quantitative ELISA study". Neuropharmacology. 56 (2): 350–361. doi:10.1016/j.neuropharm.2008.09.004. PMID 18809418. S2CID 45068116.
- ^ Fox MA, Stein AR, French HT, Murphy DL. Functional interactions between 5-HT2A and presynaptic 5-HT1A receptor-based responses in mice genetically deficient in the serotonin 5-HT transporter (SERT). Br J Pharmacol. 2010 Feb;159(4):879-87. Fox MA, Stein AR, French HT, Murphy DL (February 2010). "Functional interactions between 5-HT2A and presynaptic 5-HT1A receptor-based responses in mice genetically deficient in the serotonin 5-HT transporter (SERT)". British Journal of Pharmacology. 159 (4): 879–887. doi:10.1111/j.1476-5381.2009.00578.x. PMC 2829213. PMID 20128812.