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DASB

Chemical compound

Chemical compound

FieldValue
Verifiedfieldschanged
Watchedfieldschanged
verifiedrevid429877266
IUPAC_name3-amino-4-[2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile
imageDASB and (C-11)DASB formulas skeletal.svg
image_classskin-invert-image
captionDASB (above) and [C-11]DASB
altStructural formulas
image2(C-11)DASB molecule spacefill.png
image_class2bg-transparent
width250
caption2Radioactive carbon atom marked in cyan
alt2Space-filling model
width2220
pregnancy_AU
pregnancy_US
legal_AU
legal_CA
legal_UK
legal_US
index2_label11C-labelled
CAS_number_Ref
CAS_number627490-01-1
UNII_Ref
UNIIPP549Z0645
DrugBank_Ref
PubChem10446567
ChemSpiderID_Ref
ChemSpiderID8621986
smilesN#Cc2ccc(Sc1c(cccc1)CN(C)C)c(c2)N
CAS_number2_Ref
CAS_number2296774-13-5
UNII2_Ref
UNII2FJU46Q2BPU
PubChem2656408
ChemSpiderID2_Ref
ChemSpiderID2570800
smiles2[11CH3]N(C)Cc1ccccc1Sc2ccc(cc2N)C#N
StdInChI_Ref
StdInChI1S/C16H17N3S/c1-19(2)11-13-5-3-4-6-15(13)20-16-8-7-12(10-17)9-14(16)18/h3-9H,11,18H2,1-2H3
StdInChIKey_Ref
StdInChIKeyUVWLEPXXYOYDGR-UHFFFAOYSA-N
StdInChI2_Ref
StdInChI21S/C16H17N3S/c1-19(2)11-13-5-3-4-6-15(13)20-16-8-7-12(10-17)9-14(16)18/h3-9H,11,18H2,1-2H3/i1-1
StdInChIKey2_Ref
StdInChIKey2UVWLEPXXYOYDGR-BJUDXGSMSA-N
C16H=17N=3S=1
Note

the chemical compound

| elimination_half-life = DASB, also known as 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, is a compound that binds to the serotonin transporter. Labeled with carbon-11 — a radioactive isotope — it has been used as a radioligand in neuroimaging with positron emission tomography (PET) since around year 2000. In this context it is regarded as one of the superior radioligands for PET study of the serotonin transporter in the brain, since it has high selectivity for the serotonin transporter.

The DASB image from a human PET scan shows high binding in the midbrain, thalamus and striatum, moderate binding in the medial temporal lobe and anterior cingulate, and low binding in neocortex. The cerebellum is often regarded as a region with no specific serotonin transporter binding and the brain region is used as a reference in some studies.

Since the serotonin transporter is the target of SSRIs used in the treatment of major depression it has been natural to examine DASB binding in depressed patients. Several such research studies have been performed.

There are a number of alternative PET radioligands for imaging the serotonin transporter: [11C]ADAM, [11C]MADAM, [11C]AFM, [11C]DAPA, [11C]McN5652, and [11C]-NS 4194. A related molecule to DASB, that can be labeled with fluorine-18, has also been suggested as a PET radioligand. With single-photon emission computed tomography (SPECT) using the radioisotope iodine-123 there are further radioligands available: [123I]ODAM, [123I]IDAM, [123I]ADAM, and [123I]β-CIT. A few studies have examined the difference in binding between the radioligands in nonhuman primates, as well as in pigs.

Other compounds that can be labeled to work as PET radioligands for the study of the serotonin system are, e.g., altanserin and WAY-100635.

Methodological issues

The binding potential of DASB can be estimated with kinetic modeling on a series of brain scans.

A test-retest reproducibility PET study indicates that [11C]DASB can be used to measure the serotonin transporter parameters with high reliability in receptor-rich brain regions.

When the DASB neuroimages are analyzed the kinetic models suggested by Ichise and coworkers can be employed to estimate the binding potential. A test-retest reproducibility experiment has been performed to evaluate this approach.

Studies

Besides the studies listed below a few occupancy studies have been reported.

WhatResultSubjectsRef.DiseaseDrug/intervention
[5-HTTLPR](5-httlpr) LALA serotonin transporter genotypeIncrease in putamen43/30
[5-HTTLPR](5-httlpr) LALA serotonin transporter genotypeIncrease in midbrain19vauthors = Reimold M, Smolka MN, Schumann G, Zimmer A, Wrase J, Mann K, Hu XZ, Goldman D, Reischl G, Solbach C, Machulla HJ, Bares R, Heinz Adisplay-authors = 6title = Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotypejournal = Journal of Neural Transmissionvolume = 114issue = 5pages = 635–639date = May 2007pmid = 17225932doi = 10.1007/s00702-006-0609-0s2cid = 9369923 }}
[5-HTTLPR](5-httlpr) LALA serotonin transporter genotypeNo difference63
AgeNo effect foundvauthors = Meyer JH, Houle S, Sagrati S, Carella A, Hussey DF, Ginovart N, Goulding V, Kennedy J, Wilson AAdisplay-authors = 6title = Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudesjournal = Archives of General Psychiatryvolume = 61issue = 12pages = 1271–1279date = December 2004pmid = 15583118doi = 10.1001/archpsyc.61.12.1271author-link2 = Sylvain Houledoi-access =s2cid = 6769025author-link9 = Alan A. Wilsonauthor-link1 = Jeffrey H. Meyer }} ()
Body mass indexInverse correlation (?)?
SeasonalityHigher in winter in putamen and caudate54
SeasonalityHigher in fall and winter88
NEO PI-R NeuroticismPositive correlation in thalamus31 males
Depressed during major depressive episodesNo difference found20+20
Depressed with highly negativistic "dysfunctional attitudes" during major depressive episodesIncrease in prefrontal cortex, anterior cingulate, thalamus, bilateral caudate, and bilateral putamen20(?)+20
Recovered depressed patientsNo difference found24+20 males
Unipolar depressionIncrease in thalamus, insula and striatum18+34vauthors = Cannon DM, Ichise M, Rollis D, Klaver JM, Gandhi SK, Charney DS, Manji HK, Drevets WCdisplay-authors = 6title = Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorderjournal = Biological Psychiatryvolume = 62issue = 8pages = 870–877date = October 2007pmid = 17678634doi = 10.1016/j.biopsych.2007.03.016s2cid = 19689483 }}
Unmedicated unipolar major depressionReduced 5-HTT availability in the thalamusvauthors = Reimold M, Batra A, Knobel A, Smolka MN, Zimmer A, Mann K, Solbach C, Reischl G, Schwärzler F, Gründer G, Machulla HJ, Bares R, Heinz Adisplay-authors = 6title = Anxiety is associated with reduced central serotonin transporter availability in unmedicated patients with unipolar major depression: a [11C]DASB PET studyjournal = Molecular Psychiatryvolume = 13issue = 6pages = 606–13, 557date = June 2008pmid = 18268503doi = 10.1038/sj.mp.4002149doi-access = freeauthor-link1 = Matthias Reimold }}. Electronic publication
TCI anxiety in unmedicated unipolar major depressionReduced 5-HTT availability in the thalamus, midbrain and amygdala
Bipolar depressionIncrease in thalamus, insula and striatum18+34
Bipolar depressionDecrease in midbrain, amygdala, hippocampus, thalamus, putamen, and anterior cingulate cortex18+41
Obsessive compulsive disorderReduction and correlation with severity in thalamus and midbrain9+19
AlcoholismNo significant alteration30 + 18
Parkinson's diseaseReduction in forebrain5+8
Non-depressed Parkinson's diseaseDecreased binding in caudate, midbrain, putamen, orbitofrontal cortex and (non-significantly) dorsolateral prefrontal cortex
Depressed Parkinson's disease patientsIncrease in prefrontal and dorsolateral cortices7+7
Abstinent MDMA ('Ecstasy') usersGlobal reduction23+19
Former MDMA users and polydrug usersNo significant difference in brain regions examined12+9+19
Reduced synaptic serotonin (by rapid tryptophan depletion)(small reduction in binding potential)8
Lowering of brain serotonin (by acute tryptophan depletion)No change observed25 (14)

References

References

  1. (November 2000). "Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB". European Journal of Nuclear Medicine.
  2. (February 2006). "Neuroimaging of the Serotonin Transporter — Possibilities and Pitfalls". [[Current Psychiatry Reviews]].
  3. (July 2002). "In vitro and in vivo characterisation of [11C]-DASB: a probe for in vivo measurements of the serotonin transporter by positron emission tomography". Nuclear Medicine and Biology.
  4. (May 2006). "Estimation of serotonin transporter parameters with 11C-DASB in healthy humans: reproducibility and comparison of methods". Journal of Nuclear Medicine.
  5. (March 2007). "Imaging the serotonin transporter during major depressive disorder and antidepressant treatment". Journal of Psychiatry & Neuroscience.
  6. (September–October 2007). "3-Amino-4-(2-((4-[18F]fluorobenzyl)methylamino)methylphenylsulfanyl)benzonitrile, an F-18 fluorobenzyl analogue of DASB: synthesis, in vitro binding, and in vivo biodistribution studies". Bioconjugate Chemistry.
  7. (April 2000). "2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM): an improved serotonin transporter ligand". Nuclear Medicine and Biology.
  8. (May 2002). "Comparison of (+)-(11)C-McN5652 and (11)C-DASB as serotonin transporter radioligands under various experimental conditions". Journal of Nuclear Medicine.
  9. (November 2002). "Comparative evaluation in nonhuman primates of five PET radiotracers for imaging the serotonin transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM". Journal of Cerebral Blood Flow and Metabolism.
  10. (September 2003). "[11C]-NS 4194 versus [11C]-DASB for PET imaging of serotonin transporters in living porcine brain". Synapse.
  11. (November 2001). "Positron emission tomography quantification of [(11)C]-DASB binding to the human serotonin transporter: modeling strategies". Journal of Cerebral Blood Flow and Metabolism.
  12. (September 2003). "Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain". Journal of Cerebral Blood Flow and Metabolism.
  13. (February 2006). "PET imaging of serotonin transporters with [11C]DASB: test-retest reproducibility using a multilinear reference tissue parametric imaging method". Journal of Nuclear Medicine.
  14. (August 2007). "Novel 5-HTTLPR allele associates with higher serotonin transporter binding in putamen: a [(11)C] DASB positron emission tomography study". Biological Psychiatry.
  15. (May 2007). "Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype". Journal of Neural Transmission.
  16. (August 2010). "Serotonin transporter polymorphisms (SLC6A4 insertion/deletion and rs25531) do not affect the availability of 5-HTT to [11C] DASB binding in the living human brain". NeuroImage.
  17. (December 2004). "Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudes". Archives of General Psychiatry.
  18. (2008). "Inverse correlation between body mass index and serotonin transporter binding in human brain: A [11C]DASB PET study". NeuroImage.
  19. (June 2010). "Seasonal changes in brain serotonin transporter binding in short serotonin transporter linked polymorphic region-allele carriers but not in long-allele homozygotes". Biological Psychiatry.
  20. (September 2008). "Seasonal variation in human brain serotonin transporter binding". Archives of General Psychiatry.
  21. (September 2007). "Relationship between neuroticism personality trait and serotonin transporter binding". Biological Psychiatry.
  22. (December 2007). "5-HTT binding in recovered depressed patients and healthy volunteers: a positron emission tomography study with [11C]DASB". The American Journal of Psychiatry.
  23. (October 2007). "Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder". Biological Psychiatry.
  24. (February 2007). "Brain serotonin transporter binding in depressed patients with bipolar disorder using positron emission tomography". Archives of General Psychiatry.
  25. (December 2007). "Reduced availability of serotonin transporters in obsessive-compulsive disorder correlates with symptom severity - a [11C]DASB PET study". Journal of Neural Transmission.
  26. (January 2007). "PET [11C]DASB imaging of serotonin transporters in patients with alcoholism". Alcoholism: Clinical and Experimental Research.
  27. (March 2008). "Spared caudal brainstem SERT binding in early Parkinson's disease". Journal of Cerebral Blood Flow and Metabolism.
  28. (May 2007). "Brain serotonin transporter binding in non-depressed patients with Parkinson's disease". European Journal of Neurology.
  29. (September 2008). "Elevated serotonin transporter binding in depressed patients with Parkinson's disease: a preliminary PET study with [11C]DASB". Movement Disorders.
  30. (September 2005). "Quantitative PET studies of the serotonin transporter in MDMA users and controls using [11C]McN5652 and [11C]DASB". Neuropsychopharmacology.
  31. (April 2009). "Brain serotonin transporter binding in former users of MDMA ('ecstasy')". The British Journal of Psychiatry.
  32. (March 2005). "Effects of reduced endogenous 5-HT on the in vivo binding of the serotonin transporter radioligand 11C-DASB in healthy humans". Synapse.
  33. (November 2005). "Effects of tryptophan depletion on the serotonin transporter in healthy humans". Biological Psychiatry.
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