Nifene

{{Short description|Chemical compound}} {{drugbox | drug_name = Nifene (18F) | image = Nifene 18F.svg | image_class = skin-invert-image | IUPAC_name = 3-[(2''S'')-2,5-Dihydro-1''H''-pyrrol-2-ylmethoxy]-2-18F-fluoropyridine | synonyms =  | CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 912843-71-1 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 14VE482C8C | PubChem= 6917075 | ATC_prefix = None | C=10 | H=11 | F=1 | N=2 | O=1 | ChemSpiderID = 5292349 | smiles = C1C=C[C@H](N1)COC2=C(N=CC=C2)[18F] | StdInChI = 1S/C10H11FN2O/c11-10-9(4-2-6-13-10)14-7-8-3-1-5-12-8/h1-4,6,8,12H,5,7H2/t8-/m0/s1/i11-1 | StdInChIKey = GHHQHFNDKOQCRS-IZFLLFDKSA-N | pregnancy_category = | legal_status = Research compound }}

'''Nifene''' is a high affinity, selective nicotinic α4β2* receptor partial agonist used in medical research for nicotinic acetylcholine receptors, usually in the form of '''nifene (18F)'''<ref>{{cite journal | vauthors = Pichika R, Easwaramoorthy B, Collins D, Christian BT, Shi B, Narayanan TK, Potkin SG, Mukherjee J | display-authors = 6 | title = Nicotinic alpha4beta2 receptor imaging agents: part II. Synthesis and biological evaluation of 2-[18F]fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (18F-nifene) in rodents and imaging by PET in nonhuman primate | journal = Nuclear Medicine and Biology | volume = 33 | issue = 3 | pages = 295–304 | date = April 2006 | pmid = 16631077 | doi = 10.1016/j.nucmedbio.2005.12.017 }}</ref><ref>{{citation | vauthors = Leung K | title = 2-18FFluoro-3-2-((''S'')-3-pyrrolinyl)methoxypyridine | work = Molecular Imaging and Contrast Agent Database | year = 2004 | pmid = 20641387 }}</ref> as a positron emission tomography (PET) radiotracer.<ref>{{cite journal | vauthors = Kant R, Constantinescu CC, Parekh P, Pandey SK, Pan ML, Easwaramoorthy B, Mukherjee J | title = Evaluation of F-nifene binding to α4β2 nicotinic receptors in the rat brain using microPET imaging | journal = EJNMMI Research | volume = 1 | page = 6 | date = June 2011 | pmid = 22039577 | pmc = 3203019 | doi = 10.1186/2191-219X-1-6 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hillmer AT, Wooten DW, Slesarev MS, Ahlers EO, Barnhart TE, Murali D, Schneider ML, Mukherjee J, Christian BT | display-authors = 6 | title = PET imaging of α4β2* nicotinic acetylcholine receptors: quantitative analysis of 18F-nifene kinetics in the nonhuman primate | journal = Journal of Nuclear Medicine | volume = 53 | issue = 9 | pages = 1471–80 | date = September 2012 | pmid = 22851633 | pmc = 3580212 | doi = 10.2967/jnumed.112.103846 }}</ref>

Nifene has been used to assess the efficacy of acetylcholinesterase inhibitors in animal models, because the neurotransmitter acetylcholine competes with the binding of nifene at the nicotinic receptor site.<ref>{{cite journal | vauthors = Easwaramoorthy B, Pichika R, Collins D, Potkin SG, Leslie FM, Mukherjee J | title = Effect of acetylcholinesterase inhibitors on the binding of nicotinic alpha4beta2 receptor PET radiotracer, (18)F-nifene: A measure of acetylcholine competition | journal = Synapse | volume = 61 | issue = 1 | pages = 29–36 | date = January 2007 | pmid = 17068780 | doi = 10.1002/syn.20338 | s2cid = 85303757 }}</ref><ref>{{cite journal | vauthors = Hillmer AT, Wooten DW, Farhoud M, Higgins AT, Lao PJ, Barnhart TE, Mukherjee J, Christian BT | display-authors = 6 | title = PET imaging of acetylcholinesterase inhibitor-induced effects on α4β2 nicotinic acetylcholine receptor binding | journal = Synapse | volume = 67 | issue = 12 | pages = 882–6 | date = December 2013 | pmid = 23913347 | pmc = 3806056 | doi = 10.1002/syn.21698 }}</ref> Learning and behavior studies in animal models using nifene have suggested a potential role of the nicotinic receptors located in distinct white matter tracts.<ref>{{cite journal | vauthors = Bieszczad KM, Kant R, Constantinescu CC, Pandey SK, Kawai HD, Metherate R, Weinberger NM, Mukherjee J | display-authors = 6 | title = Nicotinic acetylcholine receptors in rat forebrain that bind 18F-nifene: relating PET imaging, autoradiography, and behavior | journal = Synapse | volume = 66 | issue = 5 | pages = 418–34 | date = May 2012 | pmid = 22213342 | pmc = 3292694 | doi = 10.1002/syn.21530 }}</ref> Nifene studies in animal models of lung cancer have suggested an upregulation of the nicotinic receptor in the lung tumors.<ref> {{cite journal | vauthors = Galitovskiy V, Kuruvilla SA, Sevriokov E, Corches A, Pan ML, Kalantari-Dehaghi M, Chernyavsky AI, Mukherjee J, Grando SA | display-authors = 6 | title = 18F-Nifene PET/CT using A/J mice treated with NNK | journal = Journal of Cancer Research & Therapy | volume = 1 | issue = 4 | pages = 128–137 | date = June 2013 | pmid = 28553544 | pmc = 5443253 | doi = 10.14312/2052-4994.2013-20 }}</ref><ref>{{cite journal | vauthors = Tang W, Kuruvilla SA, Galitovskiy V, Pan ML, Grando SA, Mukherjee J | title = Targeting histone deacetylase in lung cancer for early diagnosis: (18)F-FAHA PET/CT imaging of NNK-treated A/J mice model | journal = American Journal of Nuclear Medicine and Molecular Imaging | volume = 4 | issue = 4 | pages = 324–32 | year = 2014 | pmid = 24982818 | pmc = 4074498 }}</ref> Novel PET and SPECT imaging agents as potential receptor antagonists have been developed based on the structure of nifene; niodene for SPECT,<ref>{{cite journal | vauthors = Pandey SK, Pan S, Kant R, Kuruvilla SA, Pan ML, Mukherjee J | title = Synthesis and evaluation of 3-123I-iodo-5-[2-(S)-3-pyrrolinylmethoxy]-pyridine (niodene) as a potential nicotinic α4β2 receptor imaging agent | journal = Bioorganic & Medicinal Chemistry Letters | volume = 22 | issue = 24 | pages = 7610–4 | date = December 2012 | pmid = 23116890 | pmc = 3508149 | doi = 10.1016/j.bmcl.2012.10.012 }}</ref> nifrolene for PET <ref>{{cite journal | vauthors = Pichika R, Kuruvilla SA, Patel N, Vu K, Sinha S, Easwaramoorthy B, Narayanan TK, Shi B, Christian B, Mukherjee J | display-authors = 6 | title = Nicotinic α4β2 receptor imaging agents. Part IV. Synthesis and biological evaluation of 3-(2-(S)-3,4-dehydropyrrolinyl methoxy)-5-(3'-18F-fluoropropyl)pyridine (18F-Nifrolene) using PET | journal = Nuclear Medicine and Biology | volume = 40 | issue = 1 | pages = 117–25 | date = January 2013 | pmid = 23141552 | pmc = 3514651 | doi = 10.1016/j.nucmedbio.2012.09.009 }}</ref> and niofene for PET/SPECT.<ref>{{cite journal | vauthors = Kuruvilla SA, Hillmer AT, Wooten DW, Patel A, Christian BT, Mukherjee J | title = Synthesis and evaluation of 2-(18)F-fluoro-5-iodo-3-[2-(S)-3,4-dehydropyrrolinylmethoxy]pyridine ((18)F-Niofene) as a potential imaging agent for nicotinic α4β2 receptors | journal = American Journal of Nuclear Medicine and Molecular Imaging | volume = 4 | issue = 4 | pages = 354–64 | year = 2014 | pmid = 24982821 | pmc = 4074501 }}</ref> These new derivatives take advantage of the unique ''in vivo'' imaging properties of nifene.<ref>{{cite journal | vauthors = Hillmer AT, Wooten DW, Slesarev MS, Ahlers EO, Barnhart TE, Schneider ML, Mukherjee J, Christian BT | display-authors = 6 | title = Measuring α4β2* nicotinic acetylcholine receptor density in vivo with [(18)F]nifene PET in the nonhuman primate | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 33 | issue = 11 | pages = 1806–14 | date = November 2013 | pmid = 23942367 | pmc = 3824181 | doi = 10.1038/jcbfm.2013.136 }}</ref> Human studies with (18F)-nifene make it a promising nicotinic α4β2* receptor PET radiotracer for scientific research and has exhibited reliable test-retest reproducibility.<ref name="pmid28420041">{{cite journal | vauthors = Lao PJ, Betthauser TJ, Tudorascu DL, Barnhart TE, Hillmer AT, Stone CK, Mukherjee J, Christian BT | title = [18 F]Nifene test-retest reproducibility in first-in-human imaging of α4β2* nicotinic acetylcholine receptors | journal = Synapse | location = New York, N.Y. | volume = 71 | issue = 8 | article-number = e21981| date = August 2017 | pmid = 28420041 | pmc = 5541262 | doi = 10.1002/syn.21981 }}</ref> Human white matter thalamic radiations (or tracts) were well demarcated and quantified using (18F)-nifene.<ref name="pmid28875553">{{cite journal | vauthors = Mukherjee J, Lao PJ, Betthauser TJ, Samra GK, Pan ML, Patel IH, Liang C, Metherate R, Christian BT | title = Human brain imaging of nicotinic acetylcholine α4β2* receptors using [18 F]Nifene: Selectivity, functional activity, toxicity, aging effects, gender effects, and extrathalamic pathways | journal = The Journal of Comparative Neurology | volume = 526 | issue = 1 | pages = 80–95 | date = January 2018 | pmid = 28875553 | pmc = 5788574 | doi = 10.1002/cne.24320 }}</ref>

== References == {{Reflist|2}}

== External links == *[http://www.chemspider.com/Chemical-Structure.5292349.html ChemSpider]

Category:PET radiotracers Category:Fluoroarenes Category:Disubstituted pyridines Category:Pyrrolines