Mefway (18F)

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Mefway (18F)
Mefway 18F skeletal.svg
Systematic (IUPAC) name
4-[(18F)fluoromethyl]-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexane-1-carboxamide
Clinical data
Pregnancy cat.
  • N/A
Legal status
  • Research compound
Identifiers
CAS number 943962-60-5
ATC code None
PubChem CID 11963740
ChemSpider 10137857
Chemical data
Formula C26H35FN4O2 
Mol. mass 453.583 g/mol

Mefway is a serotonin 5-HT1A receptor antagonist used in medical research, usually in the form of mefway (18F) as a positron emission tomography (PET) radiotracer.[1] It is closely related to the research compound WAY-100,635.The compound adds a fluoromethyl group to the cyclohexyl ring of WAY-100,635.

There are two isomers with regard to the cyclohexane ring, of which the trans conformation has the higher 5-HT1A specificity.[2]

Mefway cis-trans comparison.svg

In one study the uptake and retention of mefway (18F) was found to be similar to that found for 11C-WAY-100,635. Head-to-head comparison of mefway (18F) and 11C-WAY-100,635 have been evaluated. Since 11C-WAY-100,635 is the current ‘gold standard’ and difficult to synthesize, a suitable fluorine-18 replacement as in mefway is highly desired.[3]

The ability to separately measure dissociation constant, KD and receptor density Bmax has been shown to be of potential value rather than simply comparing binding potential, Bnd. Multiple injection mefway PET experiments can be used for the in-vivo measurement of 5-HT1A receptor density.[4]

Imaging studies of mefway on in vivo and ex vivo rat brains indicate that the substance binds to the known 5-HT1A receptor regions including the dorsal raphe. These findings support that the dorsal raphe is measurable in rat PET studies.[5]

References[edit]

  1. ^ Saigal, N.; Pichika, R.; Easwaramoorthy, B.; Collins, D.; Christian, B. T.; Shi, B.; Narayanan, T. K.; Potkin, S. G.; Mukherjee, J. (2006). "Synthesis and biologic evaluation of a novel serotonin 5-HT1A receptor radioligand, 18F-labeled mefway, in rodents and imaging by PET in a nonhuman primate". Journal of nuclear medicine 47 (10): 1697–1706. PMID 17015907.  edit
  2. ^ Wooten, D.; Hillmer, A.; Murali, D.; Barnhart, T.; Schneider, M. L.; Mukherjee, J.; Christian, B. T. (2011). "An in vivo comparison of cis- and trans-[18F]mefway in the nonhuman primate". Nuclear Medicine and Biology 38 (7): 925–32. doi:10.1016/j.nucmedbio.2011.04.001. PMID 21741252.  edit
  3. ^ Wooten, D. W.; Moraino, J. D.; Hillmer, A. T.; Engle, J. W.; Dejesus, O. J.; Murali, D.; Barnhart, T. E.; Nickles, R. J.; Davidson, R. J.; Schneider, M. L.; Mukherjee, J.; Christian, B. T. (2011). "In vivo kinetics of \F-18]MEFWAY: A comparison with \C-11]WAY100635 and \F-18]MPPF in the nonhuman primate". Synapse 65 (7): 592–600. doi:10.1002/syn.20878. PMC 3080024. PMID 21484878.  edit
  4. ^ Wooten, D. W.; Hillmer, A. T.; Moirano, J. M.; Ahlers, E. O.; Slesarev, M.; Barnhart, T. E.; Mukherjee, J.; Schneider, M. L.; Christian, B. T. (2012). "Measurement of 5-HT1A receptor density and in-vivo binding parameters of \18F]mefway in the nonhuman primate". Journal of Cerebral Blood Flow & Metabolism 32 (8): 1546–1558. doi:10.1038/jcbfm.2012.43. PMC 3421091. PMID 22472611.  edit
  5. ^ Saigal, N.; Bajwa, A. K.; Faheem, S. S.; Coleman, R. A.; Pandey, S. K.; Constantinescu, C. C.; Fong, V.; Mukherjee, J. (2013). "Evaluation of serotonin 5-HT1Areceptors in rodent models using \18F]mefway PET". Synapse 67 (9): 596–608. doi:10.1002/syn.21665. PMC 3744326. PMID 23504990.  edit