| 词条 | Anabaseine |
| 释义 |
| Watchedfields = changed | verifiedrevid = 470471685 | ImageFile=Chemical Structure of Anabaseine.png | ImageName=Chemical Structure of Anabaseine | ImageSize=200px | IUPACName= | OtherNames=3,4,5,6-Tetrahydro-2,3'-bipyridin |Section1={{Chembox Identifiers | IUPHAR_ligand = 347 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID =17923 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = DYE103K23I | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = InChI=1S/C10H12N2/c1-2-7-12-10(5-1)9-4-3-6-11-8-9/h3-4,6,8H,1-2,5,7H2 | StdInChIKey = AUBPMADJYNSPOA-UHFFFAOYSA-N | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | CASNo_Ref = {{cascite|correct|CAS}} | CASNo=3471-05-4 | PubChem=18985 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = C06522 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 80787 | SMILES = C1CCC(=NC1)c1cccnc1 }} |Section2={{Chembox Properties | C=10 | H=12 | N=2 | Odor=Odorless | Appearance= Oil | Density= | BoilingPt=110-120℃ | MeltingPt= | pKa= }} |Section3={{Chembox Hazards | MainHazards= | FlashPt= | AutoignitionPt = }} }}Anabaseine (3,4,5,6-Tetrahydro-2,3’-bipyridine) is an alkaloid toxin produced by Nemertines and Aphaenogaster ants.[1] It is structurally similar to nicotine and anabasine.[2] Similarly, it has been shown to act as an agonist on most nicotinic acetylcholine receptors in the central nervous system and peripheral nervous system.[2] Mechanism of actionThe iminium form of anabaseine binds to most nicotinic acetylcholine receptors in both the peripheral nervous system and central nervous system. But, there is a higher binding affinity for receptors in the brain with a α7 subunit, as well as skeletal muscle receptors.[3] Binding causes the depolarization of neurons, and induces the release of both dopamine and norepinephrine.[2] Biological effectsAnabaseine causes paralysis in crustaceans and insects, but not in vertebrates, presumably by acting as an agonist on peripheral neuromuscular nicotinic acetylcholine receptors.[2] StructureThe anabaseine molecule consists of a non-aromatic tetrahydropyridine ring connected to the 3rd carbon of a 3-pyridyl ring. It can exist in three forms at physiological pH: a ketone, imine, or iminium structure.[2] Due to conjugation between the imine and 3-pyridyl ring, anabaseine exists as a nearly coplanar molecule. SynthesisSpath and Mamoli first synthesized anabaseine in 1936.[4] The researchers reacted benzoic anhydride with δ-valerolactam to yield N-benzoylpiperidone. Then, N-benzoylpiperidone is reacted with nicotinic acid ethyl ester to produce α-nicotinoyl-N-benzoyl-2-piperidone. This product then is decarboxylated, undergoes a ring closure, and amide hydrolysis to form anabaseine. Additional synthetic strategies have since been developed by Bloom,[5] Zoltewicz,[6] Smith,[7] and Villemin.[8] DerivativesDue to anabaseine’s fairly non-specific binding to nicotinic acetylcholine receptors, the molecule was largely discarded as a useful tool in research or medicine. However, anabaseine derivatives have been identified with a more selective α7 binding profile. One such derivative (GTS-21, 3-(2,4-dimethoxybenzylidene)-anabaseine) has been studied as a drug candidate for cognitive and memory deficits, particularly associated with schizophrenia; it has been studied in phase II clinical trials without progression to phase III.[9] Moreover, the modification of the anabaseine pyridine nucleus led to the obtainment of new derivatives endowed with binding and functional selectivity for the α3β4 nicotinic acetylcholine receptor subtype.[10] References1. ^{{cite journal|last1=Wheeler|first1=JW|last2=Olubajo|first2=O|last3=Storm|first3=CB|last4=Duffield|first4=RM|title=Anabaseine: venom alkaloid of aphaenogaster ants.|journal=Science|date=6 March 1981|volume=211|issue=4486|pages=1051–2|pmid=17744933|doi=10.1126/science.211.4486.1051}} 2. ^1 2 3 4 {{Cite journal|title = The Nemertine Toxin Anabaseine and Its Derivative DMXBA (GTS-21): Chemical and Pharmacological Properties|url = http://www.mdpi.com/1660-3397/4/3/255|journal = Marine Drugs|date = 2006-04-06|access-date = 2015-04-20|pages = 255–273|volume = 4|issue = 3|doi = 10.3390/md403255|first = William|last = Kem|first2 = Ferenc|last2 = Soti|first3 = Kristin|last3 = Wildeboer|first4 = Susan|last4 = LeFrancois|first5 = Kelly|last5 = MacDougall|first6 = Dong-Qing|last6 = Wei|first7 = Kuo-Chen|last7 = Chou|first8 = Hugo R.|last8 = Arias}} 3. ^{{cite journal|last1=Kem|first1=WR|last2=Mahnir|first2=VM|last3=Papke|first3=RL|last4=Lingle|first4=CJ|title=Anabaseine is a potent agonist on muscle and neuronal alpha-bungarotoxin-sensitive nicotinic receptors.|journal=The Journal of Pharmacology and Experimental Therapeutics|date=December 1997|volume=283|issue=3|pages=979–92|pmid=9399967}} 4. ^{{cite book|last1=Padilla|first1=Edited by Dean F. Martin [and] George M.|title=Marine pharmacognosy; action of marine biotoxins at the cellular level.|date=1973|publisher=Academic Press|location=New York|isbn=978-0124745506|pages=54–55|edition=First}} 5. ^{{cite web|last1=Bloom|first1=Linda|title=Influence of solvent on the ring-chain hydrolysis equilibrium of anabaseine and synthesis of anabaseine and nicotine analogues.|url=http://ufdc.ufl.edu/AA00004119/00001/221j|publisher=University of Florida|accessdate=5 May 2015}} 6. ^{{cite journal|last1=Zoltewicz|first1=John A.|last2=Cruskie|first2=Michael P.|title=A Superior Synthesis of Cholinergic Anabaseine|journal=Organic Preparations and Procedures International|date=August 1995|volume=27|issue=4|pages=510–513|doi=10.1080/00304949509458490}} 7. ^{{cite journal|last1=Smith|first1=Aaron|title=Synthesis and Radiolabeling of Potassium Trifluoroborate Benzilidene Anabaseine Derivatives|publisher=University of Tennessee - Knoxville}} 8. ^{{cite journal|last1=Villemin|first1=Didier|last2=Hachemi|first2=Messaoud|title=Cesium Fluoride on Calcium Oxide as a Strongly Basic Catalyst. Synthesis of Flavones and Tobacco Alkaloids|journal=Reaction Kinetics and Catalysis Letters|date=2001|volume=72|issue=1|pages=3–10|doi=10.1023/A:1010597826749}} 9. ^{{Cite book|title = Small Molecule Therapeutics for Schizophrenia|url = https://books.google.com/books?id=HEzPBAAAQBAJ&dq=GTS-21+clinical+trial+phase+III&source=gbs_navlinks_s|publisher = Springer|date = 2014-10-13|access-date = 2015-04-20|isbn = 9783319115023|first = Sylvain|last = Celanire|first2 = Sonia|last2 = Poli|page = 248}} 10. ^{{Cite journal|last=Matera|first=Carlo|last2=Quadri|first2=Marta|last3=Sciaccaluga|first3=Miriam|last4=Pomè|first4=Diego Yuri|last5=Fasoli|first5=Francesca|last6=De Amici|first6=Marco|last7=Fucile|first7=Sergio|last8=Gotti|first8=Cecilia|last9=Dallanoce|first9=Clelia|date=2016-01-27|title=Modification of the anabaseine pyridine nucleus allows achieving binding and functional selectivity for the α3β4 nicotinic acetylcholine receptor subtype|url=http://www.sciencedirect.com/science/article/pii/S0223523415303810|journal=European Journal of Medicinal Chemistry|volume=108|pages=392–405|doi=10.1016/j.ejmech.2015.11.045}} 4 : Neuropharmacology|Nicotinic agonists|Pyridine alkaloids|Drug discovery |
| 随便看 |
开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。