PK-11195

PK-11195
IUPAC name

N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide
Other names

PK-11195
Identifiers
CAS number 85340-56-3 Y
PubChem 1345
ChEMBL CHEMBL15313 N
Jmol-3D images Image 1
Properties
Molecular formula C21H21ClN2O
Molar mass 352.856 g/mol
 N (verify) (what is: Y/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

PK-11195 is an isoquinoline carboxamide which binds selectively to the peripheral benzodiazepine receptor (PBR) (also known as the mitochondrial 18 kDa translocator protein or TSPO). It is one of the most commonly used PBR ligands due to its high affinity for the PBR in all species,[1] although it is starting to be replaced by newer and more selective ligands.[2]

Early autoradiographic studies using tritiated PK-11195 ([3H]-PK11195) demonstrated that in the central nervous system (CNS) of rodent, it binds primarily to the ependymal walls, choroid plexus, and olfactory bulb. However, in the injured nervous system there is a robust and widespread increase in [3H]-PK11195 binding. The binding sites have since been determined to be on glial cells, including microglia, astrocytes, and infiltrating macrophages. The binding of [3H]-PK11195 is considered to be a useful tool in the assessment of neuronal damage.[3][4]

In addition to being a marker of neuronal damage in animal models of CNS damage, PK-11195 has been used successfully with human brain imaging techniques. [11C](R)-PK11195 has been used in positron emission tomography (PET) scanning to visualize brain inflammation in patients with neuronal damage. Increases in [11C](R)-PK11195 binding have been reported in patients with stroke, traumatic brain injury and in patients with chronic neurodegenerative conditions including Huntington's disease and Parkinson's disease.[5][6]

References

  1. ^ Pike VW, Halldin C, Crouzel C, Barré L, Nutt DJ, Osman S, Shah F, Turton DR, Waters SL (May 1993). "Radioligands for PET studies of central benzodiazepine receptors and PK (peripheral benzodiazepine) binding sites--current status". Nuclear Medicine and Biology 20 (4): 503–25. doi:10.1016/0969-8051(93)90082-6. PMID 8389223. 
  2. ^ Doorduin J, de Vries EF, Dierckx RA, Klein HC (2008). "PET imaging of the peripheral benzodiazepine receptor: monitoring disease progression and therapy response in neurodegenerative disorders". Current Pharmaceutical Design 14 (31): 3297–315. doi:10.2174/138161208786549443. PMID 19075709. 
  3. ^ Cagnin A, Gerhard A, Banati RB (December 2002). "In vivo imaging of neuroinflammation". European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology 12 (6): 581–6. PMID 12468021. 
  4. ^ Weissman BA, Raveh L (February 2003). "Peripheral benzodiazepine receptors: on mice and human brain imaging". Journal of Neurochemistry 84 (3): 432–7. doi:10.1046/j.1471-4159.2003.01568.x. PMID 12558962. 
  5. ^ Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, Piccini P (April 2007). "Imaging microglial activation in Huntington's disease". Brain Research Bulletin 72 (2-3): 148–51. doi:10.1016/j.brainresbull.2006.10.029. PMID 17352938. 
  6. ^ Bartels AL, Leenders KL (October 2007). "Neuroinflammation in the pathophysiology of Parkinson's disease: evidence from animal models to human in vivo studies with [11C]-PK11195 PET". Movement Disorders : Official Journal of the Movement Disorder Society 22 (13): 1852–6. doi:10.1002/mds.21552. PMID 17592621.