Cymserine

Cymserine

Systematic (IUPAC) name
((3aS,8aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl)-4-isopropylphenylcarbamate
Identifiers
CAS Number	145209-39-8
PubChem	CID 9907847
ChemSpider	26000641
Chemical data
Formula	C23H29N3O2
Molar mass	379.495 g/mol
SMILES C[C@@]12[C@@](N(C)CC2)([H])N(C)C3=CC=C(OC(NC4=CC=C(C(C)C)C=C4)=O)C=C31
InChI InChI=1S/C22H27N3O2/c1-14(2)15-5-7-16(8-6-15)23-22(26)27-17-9-10-20-19(13-17)18-11-12-24(3)21(18)25(20)4/h5-10,13-14,18,21H,11-12H2,1-4H3,(H,23,26)/t18-,21+/m0/s1 Key:WHFRVERUBMJQSO-GHTZIAJQSA-N
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Cymserine is a drug related to physostigmine, which acts as a reversible cholinesterase inhibitor, with moderate selectivity (15×) for the plasma cholinesterase enzyme butyrylcholinesterase, and relatively weaker inhibition of the better-known acetylcholinesterase enzyme. This gives it a much more specific profile of effects that may be useful for treating Alzheimer's disease without producing side effects such as tremors, lacrimation, and salivation that are seen with the older nonselective cholinesterase inhibitors currently used for this application, such as donepezil. A number of cymserine derivatives have been developed with much greater selectivity for butyrylcholinesterase, and both cymserine and several of its analogues have been tested in animals, and found to increase brain acetylcholine levels and produce nootropic effects, as well as reducing levels of amyloid precursor protein and amyloid beta, which are commonly used biomarkers for the development of Alzheimer's disease.^{[1][2][3][4][5][6]}

Derivatives of cymserine

References

1. Greig NH, Utsuki T, Yu Q, Zhu X, Holloway HW, Perry T, Lee B, Ingram DK, Lahiri DK. A new therapeutic target in Alzheimer's disease treatment: attention to butyrylcholinesterase. Current Medical Research and Opinion. 2001;17(3):159-65. PMID 11900310
2. Greig NH, Utsuki T, Ingram DK, Wang Y, Pepeu G, Scali C, Yu QS, Mamczarz J, Holloway HW, Giordano T, Chen D, Furukawa K, Sambamurti K, Brossi A, Lahiri DK. Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent. Proceedings of the National Academy of Sciences USA. 2005 Nov 22;102(47):17213-8. PMID 16275899
3. Kamal MA, Al-Jafari AA, Yu QS, Greig NH. Kinetic analysis of the inhibition of human butyrylcholinesterase with cymserine. Biochimica et Biophysica Acta. 2006 Feb;1760(2):200-6. PMID 16309845
4. Kamal MA, Klein P, Yu QS, Tweedie D, Li Y, Holloway HW, Greig NH. Kinetics of human serum butyrylcholinesterase and its inhibition by a novel experimental Alzheimer therapeutic, bisnorcymserine. Journal of Alzheimers Disease. 2006 Sep;10(1):43–51. PMID 16988481
5. Kamal MA, Klein P, Luo W, Li Y, Holloway HW, Tweedie D, Greig NH. Kinetics of human serum butyrylcholinesterase inhibition by a novel experimental Alzheimer therapeutic, dihydrobenzodioxepine cymserine. Neurochemical Research. 2008 May;33(5):745-53. PMID 17985237
6. Kamal MA, Qu X, Yu QS, Tweedie D, Holloway HW, Li Y, Tan Y, Greig NH. Tetrahydrofurobenzofuran cymserine, a potent butyrylcholinesterase inhibitor and experimental Alzheimer drug candidate, enzyme kinetic analysis. Journal of Neural Transmission. 2008 Jun;115(6):889-98. PMID 18235987