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Rasagiline

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a drug used in treatment of parkinsons disease

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Rasagiline

  1. 1. RASAGILINE MTI 11040 PURNIMA SINGH
  2. 2.  Parkinson's disease is a degenerative disorder of the central nervous system.  The motor symptoms of Parkinson's disease result from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain.A defect in dopamine pathway.  In Parkinson’s disease, dopamine deficiency occurs in basal ganglia.  Major pathologic process- neuronal degeneration of pigmented substantia nigra compacta (SNpc) a region of basal ganglia that produces dopamine, intrinsically involved in motor control.
  3. 3. Imbalance primarily between the excitatory neurotransmitter :Acetylcholine and the inhibitory neurotransmitter :Dopamine in the Basal Ganglia Reduction of dopamine in corpus striatum affects the balance between 2 neurotransmitters-
  4. 4. Treatment
  5. 5. RASAGILINE irreversible inhibitor of monoamine oxidase A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma Neuroprotective Agents
  6. 6. Taxonomy  Kingdom Organic Compounds  Superclass Benzenoids  Class Indanes  Direct parent Indanes
  7. 7. Structure Chemical formula- C12H13N IUPAC name- (1R)-N-prop-2-ynyl-2,3- dihydro-1H-inden-1-amine
  8. 8. Monoamine oxidase catecholamines indolamines serotonin dopamine norepinepherine norepinephrine MAO -B DOPAMINE RASAGILINE DOPAMINE
  9. 9. MAO MAO-A MAO-B MAO nerve terminals, brain, liver and intestinal mucos regulation of the metabolic degradation of dopamine
  10. 10. Dopamine is a simple organic chemical in the catecholamine family which works as a neurotransmitter DOPAC is a metabolite of the neurotransmitter dopamine which means that dopamine gets broken down into DOPAC. AADC :Aromatic L- amino decarboxylase COMT :Catechol-O- methyltransferase MAO B :Monoamine oxidase B DOPAC :3, 4- dihydroxyphenylaceti c acid One mechanism is believed to be related to its MAO-B inhibitory activity, which causes an increase in extracellular levels of dopamine in the striatum.
  11. 11. MAO-B is responsible for the breakdown of dopamine after its re-uptake from the synapse DA is taken up by D1 and D2 receptors and synapses takes place
  12. 12.  Rasagiline shows neuroprotective properties by suppressing mitochondrial apoptosis , increasing the expression of down-regulating the B-cell lymphoma 2 B-cell lymphoma- extra large Bcl-2- associated death promoter Bcl-2- associated X protein (Bax). anti- apoptotic proteins pro- apoptotic
  13. 13. stopping the translocation of glyceraldehyde-3- phosphate dehydrogenase , and halting nucleosomal DNA fragmentation stopping the mitochondrial permeability transition (MPT) pore opening by inhibiting caspase activation Neuron survives
  14. 14. Absorption  Rasagiline is rapidly absorbed following oral administration.  The absolute bioavailability of rasagiline is about 36%.  Rasagiline readily crosses the blood-brain barrier.
  15. 15. Distribution  Volume of distribution-87 L  Rasagiline is  88-94% bound to plasma proteins,  61-63% bound to human albumin over the concentration range of 1-100 ng/ml.
  16. 16. Metabolism  The metabolism of rasagiline proceeds through two main pathways:  N-dealkylation  hydroxylation to yield 1-aminoindan (AI), 3-hydroxy-N-propargyl-1 aminoindan (3-OH-PAI) and 3-hydroxy-1-aminoindan (3-OH-AI). Rasagiline CYP1A2 Hepatic Metabolism 1-aminoindan
  17. 17. Elimination  Rasagiline undergoes almost complete biotransformation in the liver prior to excretion.  Glucuronide conjugation of rasagiline and its metabolites, with subsequent urinary excretion, is the major elimination pathway.  primarily - urine  secondarily – feces  Half life of 3 hours
  18. 18. Formulations  Oral:  Tablets:  0.5 mg (of rasagiline) Azilect (Teva Neuroscience)  1 mg (of rasagiline) Azilect (Teva Neuroscience)  Storage:  15 C - 30 C
  19. 19. DOSING:  Monotherapy :The recommended dose of rasagiline is 1 mg once daily when used alone  Adjunct therapy :When combined with levodopa the recommended starting dose is 0.5 mg once daily.
  20. 20. Toxicity  drowsiness, dizziness, faintness, irritability,  hyperactivity,  agitation, severe headache, hallucinations,  coma;  rapid and irregular pulse,  hypertension, hypotension  respiratory depression and failure,  hyperpyrexia,  diaphoresis,  and cool, clammy skin.
  21. 21. Precautions  It should not be used by patients with moderate or severe liver disease.  Rasagiline should not be administered with antidepressants that increase serotonin levels - serotonin syndrome.  Rasagiline should be discontinued at least 14 days before initiating treatment with antidepressants that increase serotonin levels.
  22. 22. Recent developments  Rasagiline is being investigated for  the treatment of Restless Legs Syndrome  the treatment of Alzheimer's disease  Because of its melanin binding properties, rasagiline was investigated and found to decrease melanoma growth; it may be candidate for combination therapy for melanoma.
  23. 23. REFERENCE  www.webmd.com  http://journal.frontiersin.org/article/10.3389/fneur.2011.00068/full  www.ncbi.nlm.nih.gov/pubmed  Pharmacology of Rasagiline, a New MAO-B Inhibitor Drug for the Treatment of Parkinson’s Disease with Neuroprotective Potential , John P.M. Finberg, Ph.D.*, RMMJ|www.rmmj.org.il June 2010, Volume 1, Issue 1, e0003  The role of rasagiline in the treatment of Parkinson’s disease, Clinical Intervention in Aging, 8 May 2010.  MAO-inhibitors in Parkinson’s Disease, Peter Riederer1* and Gerd Laux2, Experimental Neurobiology , doi:10.5607/en.2011.20.1.1, Vol. 20, pages 1∼17, March 2011  Rasagiline – a novel MAO B inhibitor in Parkinson’s disease therapy, Shimon Lecht et. Al, Therapeutics and Clinical Risk Management 2007:3(3) 467–474  The neuroprotective mechanism of 1-R-aminoindan, the major metabolite of the anti- parkinsonian drug rasagiline, O.Bar-Am et al. ,journal of neurochemistry, Journal Compilation 2010 International Society for Neurochemistry, J. Neurochem. (2010) 112, 1131–1137

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