Anti Park in Son MODELS

7/31/2019 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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Anti Park in Son MODELS

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