Synthesis and Study of Anti Parkinsonism activity of 8-azabicyclo [3.2.1] octane Analogs

Abstract

Parkinson's disease (PD) is a common neurodegenerative condition associated with the degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. 3D QSAR study of 8-azabicyclo [3.2.1] octane analogs which serves as the pathfinder for the design of novel molecule for anti Parkinsonism. Five compounds of 8-azabicyclo [3.2.1] octane analogs are synthesized and the anti Parkinsonism activity and brain dopamine level were studied on albino mice. The anti Parkinsonian activity was determined by the effect of test compound A-F on drug induced catatonia using the method of Morpurgo. Atropine as well as compounds B and E significantly reduced the catatonic responses and tremors induced by chlorpromazine. The level of dopamine was measured after the administration of atropine and the test compounds in brain of mice. The study reveals that the compounds B and E have exhibited significant activity over atropine.

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S. Verma, "Synthesis and Study of Anti Parkinsonism activity of 8-azabicyclo [3.2.1] octane Analogs," Pharmacology & Pharmacy, Vol. 2 No. 2, 2011, pp. 94-99. doi: 10.4236/pp.2011.22012.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] D. M. Leod, J. Dowman, H. Hammond, T. Leete, K. Inoue and A. Abeliovich, “The Familial Parkinsonism Gene LRRK2 Regulates Neurite Process Morphology,” Neuron, Vol. 52, No. 4, 2006, pp. 587-593.
[2] A. S. Fauci, J. B. Martin, D. L. Braunwald, K. J. Kasper, S. L. Issabacher, E. Hauser, J. D. Wilson and D. L. Longo, “Harrison’s Principles of Internal Medicine,” 14th Edition, McGraw-Hill, New York, 1998, Vol. 2.
[3] N. A. Boon, N. R. Colledge, B. R. Walker and J. A. A. Hunter, “Davidson’s Principles and Practice of Medicine,” 20th Edition, Elsevier, London, 2006.
[4] A. A. Karadaghy, J. M. Lasak, J. S. Chomchai, K. M. Khan, J. Marian, M. J. Drescher and D. G. Drescher, “Quantitative Analysis of Dopamine Receptor Messages in the Mouse Cochlea,” Molecular Brain Research, Vol. 44, No. 1, 1997, pp. 151-156. doi:10.1016/S0169-328X(96)00261-6
[5] J. J. Hagan, D. N. Middlemiss, P. C. Sharpe and G. H. Poste, “Parkinson’s Disease: Prospects for Improved Drug Therapy,” Trends in Pharmacological Sciences, Vol. 18, No. 5, 1997, pp. 156-163.
[6] M. B. Stern, “Contemporary Approaches to the Pharmacotherapeutic Management of Parkinson’s Disease: An Overview,” Neurology, Vol. 40, No. 1, 1997, pp. 2-9.
[7] S. M. Verma, B. K. Razdan and D. Sasmal, “3D-QSAR Study of 8-azabicyclo[3.2.1] Octane Analogs Antagonists of Cholinergic Receptor,” Bioorganic Medicinal Chemistry Letters, Vol. 19, No. 11, 2009, pp. 3108-3112. doi:10.1016/j.bmcl.2009.03.164
[8] A. H. Blatt, “Organic Synthesis,” 2nd Edition, John Wiley & Sons, Inc., New York, Vol. 1, 1947.
[9] P. R. Mc Guirk, M. R. Jefson, D. D. Mann, N. C. Elliott, P. Chang, E. P. Cisek, C. P. Cornell, T. D. Gootz, S. L. Haskell and M. S. Hindahl, “Synthesis and Structure-Activity Relationships of 7-Diazabicyclo Alkylquinolones, Including Danofloxacin, a New Quinolone Antibacterial Agent for Veterinary Medicine,” Journal of Medicinal Chemistry, Vol. 35, No. 4, 1992, pp 611-620.
[10] P. Yogeeswari, D. Sriram, L. R. J. Suniljit, S. S. Kumar and J. P. Stables, “Anticonvulsant and Neurotoxicity Evaluation of Some 6-chlorobenzothiazolyl-2-thiosemicarbazones,” European Journal of Medicinal Chemistry, Vol. 37, No. 3, 2002, pp. 231-236. doi:10.1016/S0223-5234(02)01338-7
[11] B. K. Razdan, A. K. Sharma, K. Kumari, R. B. Bodla, B. L. Gupta and G. K. Patnaik, “Studies on Azabicyclo Systems: Synthesis and Spasmolytic Activity of Analogs of 9- methyl-3,9-diazabicyclo[4.2.1]nonane and 10-methyl-3, 10-diazabicyclo[4.3.1]decane,” European Journal of Medicinal Chemistry, Vol. 22, No. 6, 1987, pp. 573-577. doi:10.1016/0223-5234(87)90299-6
[12] C. Morpurgo, “Effect of Antiparkinson Drugs on a Phenothiazine Induced Catatonia Reaction,” Archives internationales de pharmacodynamie et de thérapie, Vol. 137, 1962, 84-90.
[13] S. K. Kulkarni, A. Arzi and P. N. Kaul, “Modification of Drug-Induced Catalepsy and Tremors by Quizapine in Rats and Mice,” Journal of Pharmacology, Vol. 30, 1980, pp. 129-135.
[14] S. K. Kulkarni, “Hand Book of Experimental Pharmacology,” Vallabh Prakashan, Delhi, 1999.
[15] M. D. E. Nerland and E. E. Smissman, “Synthesis and Evaluation of Brain Catecholamine Depletion by N-alkyl Derivatives of 6-Aminodopamine,” Journal of Medicinal Chemistry, Vol. 19, No. 1, 1976, pp 163-164. doi:10.1016/0003-2697(71)90426-X
[16] T. Nagatsu, “Biochemistry of Catecholamines, the Biochemical Method,” University Park Press, Baltimore/ London/Tokyo, 1973.
[17] A. I. Vogel, “Text Book of Quantitative Inorganic Analysis Including Elementary Instrumental Analysis,” 3rd Edition, ELBS and Longman, London, 1971.

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