PARKINSONS DISEASE

UNDER GUIDANCE OF Mr. S.B.KASTURE

PRESENTED BY- SHAIKH ARIF H. (FIRST SEMISTER M.PHARM PHARMACOLOGY)

SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH (KOPARGAON)

Definition. Dopamine synthesis. Models.

In Vitro Models.
In Vivo Models.

References.

Parkinsons disease is a degenerative disorder of CNS comprising four cardinal feature: Tremor Rigidity, Akinesia, Postural instability (TRAP)

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.

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 diseased human. Models can help observe the biochemical changes causing the disease or caused by the disease.

The In Vitro Models include the following:

Culture of Substantia Nigra. Inhibition of Apoptosis in Neuroblastoma SHSY5Y cells.

The In Vivo models includes the following:

Tremorine & Oxotremorine antagonism. MPTP models for PD.

Reserpine antagonism.
Elevated body swing test.

Purpose & Rationale:

The muscarinic agonists tremorine and oxotremorine induce parkinsonismlike 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 1822gm are used.

They are dosed orally with the standard (5mg/kg Benzatropine mesilate) & test compound 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 Slight Medium Severe

0 1 2 3
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Hypothermia: The differences of body temperature after 1, 2 and 3 hr versus basal values are summarized for each animal in the control group and the test groups. The average values are compared statistically. Tremor: The scores for all animals in each group at the three observation periods are summarized. The numbers in the treated groups are expressed as percentage of the number of the control group.
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Salivation and Lacrimation

The scores for both symptoms for all animals in each group 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 Parkinsons disease in exposed individuals.

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8 adult rhesus monkeys weighing 5-8kg were treated with MPTP (1018mg/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 (maximum severity) 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: flexed posture), 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.

Rearings and grooming episodes are recorded by an experienced observer.

Horizontal movements are recorded for 10 min.

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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, Drug Discovery 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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