Dr.

Sukanta Sen
Professor
Dept. of Pharmacology
 Neurodegenerative disorders are characterized by progressive
and irreversible loss of neurons from specific regions of the
brain.
 Prototypical neurodegenerative disorders include
 Parkinson disease (PD) and Huntington disease (HD), where
loss of neurons from structures of the basal ganglia results in
abnormalities in the control of movement;
 Alzheimer disease (AD), where the loss of hippocampal and
cortical neurons leads to impairment of memory and cognitive
ability; and
 amyotrophic lateral sclerosis (ALS), where muscular weakness
results from the degeneration of spinal, bulbar, and cortical motor
neurons.
 Currently available therapies for neurodegenerative disorders
alleviate the disease symptoms but do not alter the underlying
neurodegenerative process.
 Parkinson's disease (also known as Parkinson disease

or PD) is a degenerative disorder of the central

nervous system that often impairs the sufferer's

motor skills and speech, as well as other functions.

 Parkinson's disease belongs to a group of conditions

called movement disorders.

History of Parkinson´s disease (PD)

 First described in 1817 by an English physician,

James Parkinson, in “An Essay on the Shaking
Palsy.”

 The famous French neurologist, Charcot, further

described the syndrome in the late 1800s.
 PA R K I N S O N I S M
A slowly progressive neurodegenerative disease characterized by :
 Pill rolling tremors
 Akathisia (inability to sit still)
 Rigidity
 Kinesis(akinesia ,dyskinesia)
 Instable (stooped)
 No arm swinging in rhythm with legs,
 Sialorrhea
 Oculogyric crisis(eyes are held fixed for a variable length of
time)
 Nervous depression
 Involuntary tremors
 Seborrhea
 Masked facial expression
Parkinsonism is a clinical syndrome with 4 cardinal features:

• Bradykinesia (slowness and poverty of movement)

• Muscular rigidity

•Resting tremor (which usually abates during voluntary

movement)

• An impairment of postural balance leading to disturbances of

gait and to falling
 Alpha-synuclein - This gene has two types of mutations.
One mutation makes mutant proteins and other mutation
results on overexpression of wild type proteins (1). The
mutant forms of a-synuclein are capable of self-
aggregation and form protofibrils that can sequester
neurotoxic species, which results in dopaminergic
neuronal death.
 DJ-1 - Function of protein encoded by this gene is not
clearly understood yet. However, studies showed that
mutation in this gene results in failure of cells to protect
cell from oxidative stress mediated cell death. So the
Parkinson's disease caused by DJ-1 mutation must be
resulting from accumulation of oxidative stress.
 Parkin - A gene that codes for E3 ubiquitin-protein
ligase. Ubiquitinate cytotoxic proteins, which signals
protein complexes nearby to come and digest the substrate
proteins. Mutation in this gene results in failing to
ubiquitinate the substrate proteins, and when those
proteins accumulate, they cause dopaminergic neuronal
death.
 Ptx3 - A gene that regulates growth of dopaminergic
neurons. Ptx3 is a transcription factor that activates
cascades of genes that are specific to dopaminergic
neurons. Mutation in this gene results in improper growth
of dopaminergic neurons, which leads to Parkinson's
disease.
 It is characterized by muscle rigidity, tremor, a slowing of
physical movement (bradykinesia) and, in extreme cases, a
loss of physical movement (akinesia).

 The primary symptoms are the results of decreased

stimulation of the motor cortex by the basal ganglia,
normally caused by the insufficient formation and action
of dopamine, which is produced in the dopaminergic
neurons of the brain. Secondary symptoms may include high
level cognitive dysfunction and subtle language problems.

 PD is both chronic and progressive.

Motor symptoms
 The cardinal symptoms are (mnemonic "TRAP"):
 Tremor: normally 4-6 Hz tremor, maximal when the limb is at rest,
and decreased with voluntary movement. It is typically unilateral
at onset. This is the most apparent and well-known symptom,
though an estimated 30% of patients have little perceptible tremor;
these are classified as akinetic-rigid.
 Rigidity: stiffness; increased muscle tone. In combination with a
resting tremor, this produces a ratchety, "cogwheel" rigidity when
the limb is passively moved.
 Bradykinesia/Akinesia: respectively, slowness or absence of
movement. Rapid, repetitive movements produce a dysrhythmic and
decremental loss of amplitude.
 Postural instability: failure of postural reflexes, which leads to
impaired balance and falls.
 Other motor symptoms include:
 Gait and posture disturbances:
 Shuffling: gait is characterized by short steps, with feet barely leaving
the ground, producing an audible shuffling noise. Small obstacles tend
to cause the patient to trip.
 Decreased arm-swing.
 Turning "en bloc": rather than the usual twisting of the neck and
trunk and pivoting on the toes, PD patients keep their neck and trunk
rigid, requiring multiple small steps to accomplish a turn.
 Stooped, forward-flexed posture. In severe forms, the head and
upper shoulders may be bent at a right angle relative to the trunk
(camptocormia).
 Festination: a combination of stooped posture, imbalance, and short
steps. It leads to a gait that gets progressively faster and faster, often
ending in a fall.
  Dystonia (in about 20% of cases): abnormal, sustained, painful
twisting muscle contractions, often affecting the foot and ankle
(mainly toe flexion and foot inversion) which often interferes
with gait.
 Speech and swallowing disturbances.
 Hypophonia: soft speech. Speech quality tends to be soft, hoarse,
and monotonous. Some people with Parkinson's disease claim that
their tongue is "heavy" or have cluttered speech
 Monotonic speech.
 Festinating speech: excessively rapid, soft, poorly-intelligible
speech.
 Drooling: most likely caused by a weak, infrequent swallow and
stooped posture.
 Non-motor causes of speech/language disturbance in both
expressive and receptive language: these include decreased verbal
fluency and cognitive disturbance especially related to
comprehension of emotional content of speech and of facial
expression.
  Dysphagia: impaired ability to swallow. Can lead to aspiration,
pneumonia
 Other motor symptoms:
 Fatigue(up to 50% of cases);
 Masked faces (a mask-like face also known as hypomimia),
with infrequent blinking;
 Difficulty rolling in bed or rising from a seated position;
 Micrographia (small, cramped handwriting);
 Impaired fine motor dexterity and motor coordination;
 Impaired gross motor coordination;
 Poverty of movement: overall loss of accessory movements,
such as decreased arm swing when walking, as well as
spontaneous movement;
 Akathisia.
 Cognitive disturbances
 Slowed reaction time; both voluntary and involuntary motor responses are
significantly slowed.

 Executive dysfunction, characterized by difficulties in: differential allocation of

attention, impulse control, set shifting, prioritizing, evaluating the salience of
ambient data, interpreting social cues, and subjective time awareness. This
complex is present to some degree in most Parkinson's patients; it may progress to:

 Dementia: a later development in approximately 20-40% of all patients, typically

starting with slowing of thought and progressing to difficulties with abstract
thought, memory, and behavioral regulation. Hallucinations, delusions and
paranoia may develop.

 Short term memory loss; procedural memory is more impaired than declarative
memory. Prompting elicits improved recall.
 Autonomic disturbances
 Oily skin and seborrheic dermatitis
 Urinary incontinence, typically in later disease progression
 Nocturia (getting up in the night to pass urine) — up to 60% of
cases
 Constipation and gastric dysmotility that is severe enough to
endanger comfort and even health
 Altered sexual function: characterized by profound impairment of
sexual arousal, behavior, orgasm, and drive is found in mid and late
Parkinson disease. Current data addresses male sexual function
almost exclusively.
 Weight loss, which is significant over a period of ten years.
Epidemiology of PD

 The most common movement disorder

affecting 1-2 % of the general
population over the age of 65 years.

 The second most common

neurodegenerative disorder after
Alzheimer´s disease (AD).
 Incidence of PD PD
Incidence / 100 000

Age
 Diagnosis:
-18F PET scan shows decreased dopamine activity
in the basal ganglia a pattern which aids in
diagnosing Parkinson's disease .
 Pathology:
 The symptoms of Parkinson's disease result from the loss of
pigmented dopamine-secreting (dopaminergic) cells in the pars
compacta region of the substantia nigra (literally "black
substance").

 These neurons project to the striatum and their loss leads to

alterations in the activity of the neural circuits within the basal
ganglia that regulate movement, in essence an inhibition of the
direct pathway and excitation of the indirect pathway.
 Parkinson’s disease is one of the most common
neurodegenerative diseases, affecting about 1% of all
people over the age of 65.
 It affects the Pope, Michael J. Fox and Muhammad
Ali. The main symptoms include:
1. Tremor at rest, usually starting in the hands that tends to
diminish during voluntary activity,
2. Muscle rigidity,
3. Suppression of voluntary movements, movement is
difficult to stop as well as start.
4. Speech difficulties,
5. Muscle weakness,
Figure Schematic wiring diagram of the basal ganglia. The striatum is the
principal input structure of the basal ganglia and receives excitatory
glutamatergic input from many areas of cerebral cortex. The striatum
contains projection neurons expressing predominantly D1 or D2
dopamine receptors, as well as
interneurons that use ACh as a neurotransmitter. Outflow from the
striatum proceeds along 2 routes.
The direct pathway, from the striatum to the substantia nigra pars
reticulata (SNpr) and globus pallidus interna (GPi), uses the inhibitory
transmitter GABA. The indirect pathway, from the striatum through the
globus pallidus externa (GPe) and the subthalamic nucleus (STN) to the
SNpr and GPi, consists of 2 inhibitory GABA-ergic links and 1 excitatory
glutamatergic projection (Glu). The substantia nigra pars compacta
(SNpc) provides dopaminergic innervation to the striatal neurons, giving
rise to both the direct and indirect pathways, and regulates the relative
activity of these 2 paths. The SNpr and GPi are the output structures of
the basal ganglia and provide feedback to the cerebral cortex through the
ventroanterior and ventrolateral nuclei of the thalamus (VA/VL).
Figure The basal ganglia in Parkinson disease. The primary defect is
destruction of the dopaminergic neurons of the SNpc. The striatal
neurons that form the direct pathway from the striatum to the SNpr and
GPi express primarily the excitatory D1 DA receptor, whereas the striatal
neurons that project to the GPe and form the indirect pathway express
the inhibitory D2 dopamine receptor. Thus, loss of the dopaminergic
input to the striatum has a differential effect on the 2 outflow pathways;
the direct pathway to the SNpr and GPi is less active (structures in
purple), whereas the activity in the indirect pathway is increased
(structures in red). The net effect is that neurons in the SNpr and GPi
become more active. This leads to increased inhibition of the VA/VL
thalamus and reduced excitatory input to the cortex. Light blue lines
indicate primary pathways with reduced activity.
 PD is often idiopathic, but it may follow stroke, virus
infection or can be drug-induced (antipsychotic drugs).

 PD is associated with early degeneration of

dopaminergic nigrostriatal neurons, followed by more
general neurodegeneration.
 PD can be induced by MPTP, a neurotoxin affecting
dopamine neurons. Similar environmental neurotoxins, as
well as genetic factors, may be involved in human PD.
 The intrinsic cholinergic neurons of the corpus striatum (which has the
highest content of acetylcholine, CAT and acetylcholinesterase in the brain)
are also involved in PD (as well as Huntington's disease).

 Acetylcholine release from the striatum is strongly inhibited by

dopamine, and it is suggested that hyperactivity of these cholinergic
neurons (associated with the lack of dopamine) leads to the symptoms of
PD, whereas hypoactivity (associated with a surfeit of dopamine, secondary
to a deficiency of GABA) results in the hyperkinetic movements and
hypotonia characteristic of Huntington's disease.

 In both conditions, therapies aimed at redressing the balance between the

dopaminergic and cholinergic neurons are, up to a point, beneficial.
 Drug therapy for Parkinson’s disease:
1)Drugs affecting brain dopaminergic system:
(a) Dopamine precursor : Levodopa

(b) Peripheral decarboxylase inhibitors: Carbodopa, Benserazide

(c) Dopaminergic agonists : Bromcriptine, pergolide, lisuride, caberoline,

Ropinirole, Pramipexole

(d) MAO-B inhibitors: Selegiline, Rasagiline

(e) COMT (catechol-o-methyl transferase) inhibitors : Entacapone,

Tolcapone
(f) Dopamine facilitator: Amantadine
2) Drugs affecting brain cholinergic system:
(a) Central anticholinergics: Trihexyphenidyl, Procyclidine,
Benztropine, Beperiden
 Drugs provide symptomatic relief by restoring dopaminergic &
cholinergic balance.
LEVODOPA
 Inactive by itself
 Is the immediate precursor of DA.
 95% of oral dose decarboxylated in the peripheral tissues
 1-2% of administered L-dopa crosses BBB
 High first-pass metabolism
 Metabolites are excreted in urine after conjugation.
Actions:
 single most effective agent in the treatment of PD
 CNS- Hypokinesia & rigidity resolve first, later tremor as
well.
 CVS: Tachycardia(β receptors),postural hypotension(d/t central
or ganglionic action).
 CTZ: N/V by stimulating D2 receptors [Q]
 Endocrine: inhibit prolactin release.
 A common problem is the development of the "wearing off"
phenomenon: each dose of levodopa effectively improves
mobility for a period of time, perhaps 1 to 2 hours, but rigidity
and akinesia return rapidly at the end of the dosing interval.

 Increasing the dose and frequency of administration can

improve this situation, but this often is limited by the
development of dyskinesias, excessive and abnormal involuntary
movements.
 An important unanswered question regarding the use of
levodopa in PD is whether this medication alters the course
of the underlying disease or merely modifies the symptoms.

 Two aspects of levodopa treatment and the outcome of PD are of

concern.

 First, if the production of free radicals as a result of dopamine

metabolism contributes to the death of nigrostriatal neurons,
then the addition of levodopa actually might accelerate the
process, although no convincing evidence for such an effect has
yet been obtained.
 Second, it is well established that the undesirable on/off

fluctuations and wearing off phenomena are observed

almost exclusively in patients treated with levodopa, but it is

not known if delaying treatment with levodopa will delay the

appearance of these effects.

 Periphery Brain
3-OMD B-B-B 3-OMD
Tolcapone
Entacapone(-) COMT TOLCAPONE(-)
Levodopa Levodopa
Carbidopa DDC
Benserazide DDC
(-) Dopamine
COMT MAO-B
3-MT DOPAC
Dopamine MAO-B COMT

HVA
Pharmacological preservation of L-DOPA and striatal dopamine:
The principal site of action of inhibitors of COMT (e.g., tolcapone
and entacapone) is in the peripheral circulation. They block the O-
methylation of L-dopa and increase the fraction of the drug
available for delivery to the brain.

Tolcapone also has effects in the CNS. Inhibitors of MAO-B, such

as low-dose selegiline and rasagiline, will act within the CNS to
reduce oxidative deamination of DA, thereby enhancing vesicular
stores.

AADC, aromatic L-amino acid decarboxylase; DA, dopamine;

DOPAC, 3,4-dihydroxyphenylacetic acid; MAO, monoamine
oxidase; 3MT, 3-methoxyltyramine; 3-OMD, 3-Omethyl DOPA.
Drug Interactions:
 Pyridoxine enhances the exacerbated metabolism of levodopa
& decreases/abolishes therapeutic effects.
 MAO-Inhibitors potentiate the toxicity of levodopa
(hypertensive crisis)
S/Es:
1) Nausea & vomiting
2) Postural hypotension
3) Cardiac arrhythmias
4) Exacerbations of angina
5) Alteration of taste sensation
6) Abnormal movements- facial tics etc.
7) Behavioral changes
8) Fluctuations of motor performance
9) Induction of hallucinations and confusion
 Peripheral decarboxylation of levodopa and release of dopamine into the
circulation may activate vascular dopamine receptors and produce
orthostatic hypotension.

 The actions of dopamine at alpha and beta adrenergic receptors may

induce cardiac arrhythmias, especially in patients with pre-existing
conduction disturbances.

 Administration of levodopa with nonspecific inhibitors of MAO, such as

phenelzine and tranylcypromine, markedly accentuates the actions of
levodopa and may precipitate life-threatening hypertensive crisis
and hyperpyrexia; nonspecific MAO inhibitors always should be
discontinued at least 14 days before levodopa is administered.
CARBIDOPA & BENSERAZIDE (Peripheral carboxylase
inhibitors):
 Prevent peripheral degradation of Levodopa
 Plasma t1/2 of levodopa is prolonged
 Systemic conc. of DA is reduced-N/V is reduced
 Lowers the dose requirement
 “On-off” effect is minimized
 Cardiac complications are minimized
 Better degree of improvement

But–accentuated involuntary movements, behavioral abnormalities

& postural hypotension.
Dopamine agonists:
 Directly stimulates DA receptors

 Do not depend on formation of dopamine

 Do not depend on the functional integrity of nigrostraital

dopaminergic pathway.

 Have longer duration of action than levodopa

 Lesser dyskinesia & “on-off’ phenomenon

 More selective

 Are less likely to generate damaging free radicals

 Dopamine agonists readily cross the blood-brain barrier and act
directly on postsynaptic dopamine receptors (primarily D2
type).

 Compared to levodopa, they are longer-acting and thus provide a

more uniform stimulation of dopamine receptors.

 They are effective as mono-therapeutic agents and as adjuncts to

carbidopa/levodopa therapy.

 They can also be used in combination with anti-cholinergics and

amantadine.
 Four orally administered dopamine-receptor agonists are
available for treatment of PD: two older agents, bromocriptine
and pergolide ; and

 two newer, more selective compounds, ropinirole and

pramipexole.

 Bromocriptine and pergolide both are ergot derivatives and

share a similar spectrum of therapeutic actions and adverse
effects.
 Bromcriptine,pergolide,lisuride and cabergoline are ergot
derivatives which share DA like structure.
 Pramipexole & ropinirole are new non-ergot DA receptor
agonists.
 Non-ergot agonists provide rapid achievement of therapeutic
response & are better tolerated.
 Bromcriptine- potent D2 receptor agonist & a weak D1
antagonist.
 Pergolide –a potent D1,D2 & D3 receptor agonist .
 Lisuride more potent, D2 agonist& 5-HT agonist.
 Cabergoline is like bromcriptine but longer acting.
 Ropinirole & pramipexole are D2, D3 & D4 agonists.
 if the hypothesis that free radical formation as a result of
dopamine metabolism contributes to neuronal death is
correct, then dopamine-receptor agonists may have the
potential to modify the course of the disease by reducing
endogenous release of dopamine as well as the need for
exogenous levodopa.
 The introduction of pramipexole and ropinirole has led to a
substantial change in the clinical use of dopamine agonists in
PD. Because these selective agonists are well tolerated, they are
used increasingly as initial treatment for PD rather than as
adjuncts to levodopa.

 This change has been driven by two factors:

(1) the belief that because of their longer duration of action,

dopamine agonists may be less likely than levodopa to
induce on/off effects and dyskinesias and

(2) the concern that levodopa may contribute to oxidative stress,

thereby accelerating loss of dopaminergic neurons.
 Apomorphine is a dopaminergic agonist that can be
administered by subcutaneous injection.

 It has high affinity for D4 receptors; moderate affinity for D2,

D3, D5, and adrenergic a1D, a2B, and a2C receptors; and low
affinity for D1 receptors.

 Apomorphine has been approved recently by the U.S. Food and

Drug Administration (FDA) as a "rescue therapy" for the
acute intermittent treatment of "off" episodes in patients
with a fluctuating response to dopaminergic therapy.
 COMT INHIBITORS:
 COMT metabolises catecholamines including DA & its
precusor levodopa, producing inactive metabolite 3-O-
methylopa.
 Adjuvants to levodopa-carbidopa combination----selective
COMT inhibitors such as tolcapone/entacapone not only
diminish peripheral metabolism of levodopa but also increase
its BA in the brain.
 Tolcapone has both central & peripheral effects while
entacapone is a peripheral blocker of COMT.
 S/Es: dyskinesias, nausea, diarrhoea, postural hypotension,
sleep disturbances & hepatotoxicity.
Inhibition of peripheral COMT by entacapone increases the
amount of L-DOPA and dopamine in the brain and improves
the alleviation of PD symptoms.
 MAO-B inhibitors:
 Irreversible inhibitor of MAO-B,an enzyme responsible for the
metabolism of dopamine.
 MAO-B is the principal enzyme present in the dopaminergic
neurons of the striatum.
 May retard progression of PD by reducing oxidative damage d/t
the formation of free radicals produced during the metabolism of
dopamine (neuroprotective role).
 Neuroprotective & anti-apoptotic effects of selegiline are related
to its metabolite desmethylselegiline.
 Has little effect on MAO-A & does not cause HT a/w the ingestion
of tyramine–enriched food (CHEESE REACTION).
 Rasagiline:
 is similar to selegiline,but is more potent.
 It prevents formation of neurotoxin MPP+ from MPTP & thus
provides neuroprotective effects in patients of PD.
AMANTADINE(DOPAMINE FACILITATOR):
 An antiviral drug.
 It seems that----------
(1) the drug prevents DA uptake.
(2) facilitates presynaptic DA release,
(3) possesses weak antimuscarinic actions
(4) blocks glutamate NMDA receptor.
 Is probably best used ---(a) alone to treat early stage PD or in
patients who does not respond well to levodopa.
(b) in combination with levodopa+carbidopa.
S/Es
 Nausea,dizziness,insomnia,hallucinations,ankle oedema & livedo
reticularis(discoloured area of skin d/t passive congetion).
Q. CENTRALLY ACTING ANTIMUSCARINIC DRUGS:
 Blockade of central muscarinic receptors reduces striatal
cholinergic activity. Antagonists of muscarinic acetylcholine
receptors were used widely for the treatment of PD before the
discovery of levodopa.

 Several drugs with anticholinergic properties currently are used in

the treatment of PD, including trihexyphenidyl, benztropine
mesylate, and diphenhydramine hydrochloride (BENADRYL).
 Diphenhydramine also is a histamine H1 antagonist. All have
modest antiparkinsonian activity that is useful in the treatment
of early PD or as an adjunct to dopamimetic therapy.

 Most commonly used to treat –

(1) early stage of disease

(2) late stage of PD with levodopa+carbidopa

(3) neuroleptic induced extrapyramidal S/Es

S/Es: dry mouth, blurred vision, urinary retention, constipation,

confusion & delirium
 Neuroprotective Therapy:
 Epidemiologic studies suggest that the chronic use of
nonsteroidal anti-inflammatory agents or the use of
estrogen replacement in postmenopausal women may delay
or prevent the onset of PD through yet-unclear mechanisms.

 Coenzyme Q10, an antioxidant and a cofactor of complex I of

the mitochondrial oxidative chain, has been shown to have
neuroprotective effects against multiple toxic agents in vitro
and in animal models of PD.
Dopamine agonist or L-DOPA+Carbidopa
Inadequate control

Add L-DOPA plus carbidopa

Inadequate control
& wearing off

L-Dopa +carbidopa dosed more frequently or

With higher dose
Inadequate control
& wearing off
Add COMT inhibitor or add MAO-B inhibitor

Adjunct therapy:
For tremor: add anti-cholinergic
For drug induced dyskinesias: add amantadine
For freezing “off” episode: add Apomorphine
Failed maximal
Medical therapy
Consider surgical option
 All of the following statements regarding interactions
of Levodopa are correct except (AIPGME 04)
1. It is a prodrug
2. In Parkinsonism, phenothiazines reduce its efficacy
3. Pyridoxine reduces effect of levodopa in parkinsonism
4. Domperidone blocks levodopa induced emesis and its
therapeutic potential
 Monitoring of drug level is not needed with which of
the following drugs (Jipmer02)
1. Lithium
2. L-Dopa
3. Digoxin
4. Phenytoin
 Conventional antipsychotic agents, such as the
phenothiazines, are effective against levodopa-induced
psychosis but may cause marked worsening of
parkinsonism, probably through actions at the
D2 dopamine receptor.

 A recent approach has been to use the "atypical"

antipsychotic agents, which are effective in the treatment
of psychosis but do not cause or worsen parkinsonism .
The most effective of these are clozapine and quetiapine.
 L-dopa is given along with Carbidopa (AIPGME
94)
1. To prevent peripheral decarboxylation of L-dopa
2. To reduce side effects
3. To increase compliance
4. To increase half-life
 False statement about Selegiline is (AIPGME 01)
1. It is a MAO-A inhibitor
2. Does not cause cheese reaction
3. May be used in on-off phenomenon
4. It is used in parkinsonism
 A patient of Parkinsonism is managed with L-dopa. If
Vit.B-complex is administered concurrently
(AIPGME2000)
1. The action of L-dopa in brain will be potentiated
2. Decarboxylation of L-dopa in brain will be decreased
3. Side-effects will be ameliorated
4. Decreased efficacy will result
 Clinically significant drug interaction occurs between
pyridoxine and all the following drugs except
(AIPGME 04)
1. Isoniazid
2. Cyclosporine
3. Levodopa
4. Hydralazine
 Ropinirole is the most useful for the treatment of
(AIIMS 04)
1. Wilson’s disease
2. Parkinson’s disease
3. Hoffman’s syndrome
4. Carpal tunnel syndrome
 Mechanism of action of Bromcriptine is (Jipmer 95)
1. Action of post-synaptic dopamine receptors
2. Inhibition of hydrolysis of dopamine
3. Inhibition of reuptake
4. Increase dopamine synthesis
 Which of the following is not an effect of Bromcriptine
(AIIMS 95)
1. Dopamine agonist
2. Increases prolactin release
3. Decreases prolactin release
4. All of the above
 All are true about Bromocriptine, except
(UPPGME 04)
1. Dopamine agonist
2. Increases prolactin level
3. Decreased gastrointestinal motility
4. Metabolites are excreted mainly in bile
 Bromocriptine is not used in (AIIMS 97)
1. Induction of ovulation
2. Galactorrhea
3. Post pill amenorrhea
4. Luteal phase defect
 Bromocriptine is useful in all of the following, except
(AIPGME 89)
1. Endogenous depression
2. Parkinsonism
3. Infertility
4. Acromegaly
 Selegilline is a selective inhibitor of (AIPGME 99)
1. MAO-A
2. MAO-B
3. Dopamine
4. Norepinephrine –uptake
 Baclofen acts as (PGI 2000)
1. GABAA receptor agonist
2. GABAB receptor agonist
3. GABAA receptor antagonist
4. GABAB receptor antagonist
 Baclofen is given in (CUPGEE 01)
1. Cerebral palsy
2. Infective polyneuritis
3. C-J disease
4. Cerebral tumors
 Drug causing Parkinsonism is (DNB 01)
1. Promethazine
2. Amiodarone
3. Bromcriptine
4. Metoclopramide
 Antipsychotic drug induced Parkinsonism is treated by
(AIPGME 05)
1. Levodopa
2. Selegiline
3. Amantadine
4. Anticholinergics
 The drug induced Parkinsonism is best treated with
(UPPGME 96)
1. Deprenyl
2. Benzhexol
3. Levodopa
4. Procyclidine
 Drug of choice in drug induced Parkinsonism
(UPPGME 08)
1. Levodopa
2. Benzhexol
3. Selegilline
4. Amantadine
 Hyperprolactinemia is a side effect of (DNB
2000)
1. Bromocriptine
2. Levodopa
3. Amantadine
4. Metoclopramide
 Which of the following drug is contraindicated in
Parkinsonism (UPPGME 03)
1. Anticholinergic
2. Amoxapine
3. Carbidopa
4. Salicylates
 All of the following may cause Neuroleptic malignant
syndrome, except (AIIMS, Nov08)
1. Domperidone
2. Metoclopramide
3. Haloperidol
4. Amantadine
 Drug used in Alzheimer’s disease having adverse effect
on liver is (Jipmer 04)
1. Tacrine
2. Donepezil
3. Thioctic acid
4. Flumazenil
THANK YOU