anti park in son models
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UNDER GUIDANCE OF Mr. S.B.KASTURE
PRESENTED BY- SHAIKH ARIF H.
(FIRST SEMISTER M.PHARM
PHARMACOLOGY)
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH
(KOPARGAON)
PARKINSONS DISEASE
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Definition.
Dopamine synthesis.
Models.
In Vitro Models.
In Vivo Models.
References.
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Parkinsons disease is a degenerative disorder
of CNS comprising four cardinal feature:
Tremor
Rigidity,
Akinesia,
Postural instability (TRAP)
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NORMAL PARKINSONS DISEASE
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Definite: Old age.
Probable: Positive family history.
Possible: Herbicides, pesticides, heavy metals,
proximity to industry, rural residence, well water,
repeated head trauma, etc.
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Models are required for screening the Anti PD
Drug.
Models are the replica of the disease state in
human i.e. models are the replica of the diseasedhuman.
Models can help observe the biochemical
changes causing the disease or caused by the
disease.
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The In Vitro Models include the following:
Culture of Substantia Nigra.
Inhibition of Apoptosis in Neuroblastoma SH-
SY5Y cells.
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The In Vivo models includes the following:
Tremorine & Oxotremorine antagonism.
MPTP models for PD.
Reserpine antagonism.
Elevated body swing test.
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Purpose & Rationale:
The muscarinic agonists
tremorine and oxotremorine induce parkinsonism-like signs such as tremor, ataxia, spasticity, salivation,
lacrimation and hypothermia. These signs are
antagonized by anticholinergic drugs.
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6-10 NMRI mice weighing 18-22gm are used.
They are dosed orally with the
standard (5mg/kg
Benzatropine mesilate) & testcompound 1 hr. prior to
administration of 0.5mg/kg
Oxotremorine s.c.
Rectal temp. is measured
before administration of the
compound(Basal value) & 1, 2 &
3 hr. after oxotremorine
injection.
Tremor is scored after
oxotremorine dosage in 10-s
observation periods every
15min for 1 h.
Salivation and lacrimation are
scored 15 and 30min after
oxotremorine injection.
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Absent 0
Slight 1
Medium 2
Severe 3
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Hypothermia:
The differences of body temperatureafter 1, 2 and 3 hr versus basal values aresummarized for each animal in the control groupand the test groups. The average values are
compared statistically. Tremor:
The scores for all animals in each group atthe three observation periods are summarized.
The numbers in the treated groups are expressedas percentage of the number of the controlgroup.
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Salivation and Lacrimation
The scores for both symptoms for all animals in eachgroup are summarized at the two observation periods.
The numbers in the treated groups are expressed as a
percentage of the number of the control group.
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PURPOSE AND RATIONALE
MPTP (N-methyl-4-phenyl-1,2,3,6tetrahydropyridine)
has been shown to cause symptoms of Parkinsonsdisease in exposed individuals.
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8 adult rhesus monkeys
weighing 5-8kg were
treated with MPTP (10-
18mg/kg, i.v.) over a
period of 5-8 days.
The animals showed a
Parkinsons like disorder
which was reveresed by
L-Dopa administration.
The pathological &
biochemical changes
produced by MPTP were
similar to the patient with
PD.
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The severity of parkinson symptoms is rated by trained
observers using a scale of 0 (normal) to 17 (maximumseverity) that assesses:
Movement (0: normal;1: reduced; 2: sleepy),
Checking movements (0: present; 1: reduced; 2: absent),
Attention and blinking (0: normal; 1: abnormal), Posture (0: normal; 1: abnormal trunk; 2: abnormal trunk
and tail; 3: abnormal trunk, tail, and limbs; 4: flexedposture),
Balance and coordination (0: normal; 1: impaired; 2:
unstable; 4: falls),
Reactions (0: normal; 1: reduced; 2: slow; 3: absent)
Vocalizations (0: normal; 1: reduced; 2: absent).
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PURPOSE AND RATIONALE:
Reserpine induces depletion of central
catecholamine stores.
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Male NMRI mice
weighing 20-25 gm
are injected by
Reserpine (5mg/kg,
i.p.) before 24 hr of
expt.
The test compound is
injected 30 minute
prior to observation.
The animals are placed
singly onto the floor of
a Perspex container(30
26 cm, 20 cm high),
situated on a Panlab
proximity sensor unit.
Horizontal
movements are
recorded for 10 min.
Rearings andgrooming episodes
are recorded by an
experienced observer.
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Locomotor activity and grooming scores
of drug treated animals are compared
with controls treated with reserpine and
vehicle only by analysis of variance.
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1. Goodman & Gilmons, The Pharmacological Basis Of
Therapeutics. By Laurence L. Brunton, John S. Lazo. Keith L.
Parker, 11th edition;934-961
H. Gerhard Vogel(Ed.), 2008; Second Edition, DrugDiscovery and Evaluation Pharmacological Assays,Springer Publication Page : 820-822, 824-829.
K. D. Tripathi,2009; Sixth Edition, Essentials of Medical
Pharmacology. Jaypee Brothers Medical Publishers,Page : 416.
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