a drug used in treatment of parkinsons disease

1. RASAGILINE
MTI 11040
PURNIMA SINGH

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.

5. 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-

6. Treatment

7. 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

8. Taxonomy
 Kingdom Organic Compounds
 Superclass Benzenoids
 Class Indanes
 Direct parent Indanes

9. Structure
Chemical
formula-
C12H13N
IUPAC name-
(1R)-N-prop-2-ynyl-2,3-
dihydro-1H-inden-1-amine

10. Monoamine
oxidase
catecholamines
indolamines serotonin
dopamine
norepinepherine
norepinephrine
MAO -B DOPAMINE
RASAGILINE DOPAMINE

11. MAO
MAO-A
MAO-B
MAO
nerve terminals,
brain, liver and
intestinal mucos
regulation of the
metabolic
degradation of
dopamine

12. 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.

13. 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

14.  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

15. 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

16. Absorption
 Rasagiline is rapidly absorbed following
oral administration.
 The absolute bioavailability of rasagiline is
about 36%.
 Rasagiline readily crosses the blood-brain
barrier.

17. 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.

18. 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

19. 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

20. Formulations
 Oral:
 Tablets:
 0.5 mg (of rasagiline) Azilect (Teva Neuroscience)
 1 mg (of rasagiline) Azilect (Teva Neuroscience)
 Storage:
 15 C - 30 C

21. 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.

22. 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.

23. 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.

24. 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.

25. 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