ArifPresentation1

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UNDER THE GUIDANCE OF Mr.S.B.KASTURE BY SHAIKH ARIF H. (FIRST SEMISTER- PHARMACOLOGY) UNDER GUIDANCE OF Dr. S.B.KASTURE PRESENTED BY- ARIF SHAIKH (FIRST SEMISTER M.PHARM PHARMACOLOGY) SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH (KOPARGAON) PRECLINICAL EVALUATION OF ANTI-PARKINSON’S 1

CONTENT : 

Defination Clinical feature Causes Pathophysiology Classification Animal models Reference 2 CONTENT

DEFINATION : 

It is neurodegenerative disorder of CNS. Associated with neurological consequences of decreased dopamine levels produced by the basal ganglia (substantia nigra) (SN) Dopamine is a neurotransmitter found in the neural synapses in the brain. Normally, neurones from the SN supply dopamine to the corpus striatum (controls unconscious muscle control) Dopamine (inhibitory) & Ach (excitatory) 3 DEFINATION

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Four Cardinal symptoms: Tremor Rigidity, Akinesia, Postural instability (TRAP) 4 CLINICAL FEATURE

CAUSES : 

Unclear, but is a number of factors: Environmental – toxins Free Radicals Aging – age related decline in dopamine production Genetic . 5 CAUSES

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WHAT HAPPEN IN PARKINSON? 6

PATHOPHYSIOLOGY : 

7 PATHOPHYSIOLOGY Degeneration of neurones in the substantia nigra (SN) Degeneration of nigrostriatal (dopaminergic) tract Results in deficiency of Dopamine in Striatum - >80%

HOW CELL DEATH IS OCCUR : : 

8 HOW CELL DEATH IS OCCUR : Environmental Toxins Neuronal Metabolism Aging Free radical formation, stress, excitotoxicity DNA Damage Lipid peroxidation Protein Damage Cell Death

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TREATEMENT 9

CLASSIFICATION : 

Drugs acting on dopaminergic system: Dopamine precursors – Levodopa (l-dopa) Peripheral decarboxylase inhibitors – carbidopa and benserazide Dopaminergic agonists: Bromocriptyne, Ropinirole and Pramipexole MAO-B inhibitors – Selegiline, Rasagiline COMT inhibitors – Entacapone, Tolcapone Dopamine facilitator - Amantadine Drugs acting on cholinergic system Central anticholinergics – Procyclidine, Biperiden, etc 10 CLASSIFICATION

MODE OF ACTION OF DRUGS : 

11 MODE OF ACTION OF DRUGS

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Result 12

MODELS FOR PARKINSON DISEASE : 

Models are required for screening the Anti PD Drug. Models can help observe the biochemical changes caused by the disease. 13 MODELS FOR PARKINSON DISEASE

IN VITRO MODELS : 

The In Vitro Models include the following: Culture of Substantia Nigra. Inhibition of Apoptosis in Neuroblastoma SH-SY5Y cells. 14 IN VITRO MODELS

IN VIVO MODELS : 

The In Vivo models includes the following: Tremorine & Oxotremorine antagonism. MPTP models for PD. Reserpine antagonism. Elevated body swing test. 15 IN VIVO MODELS

TREMORINE & OXOTREMORINE ANTAGONISM : 

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. 16 TREMORINE & OXOTREMORINE ANTAGONISM

PROCEDURE : 

17 PROCEDURE

SCORING FOR TREMOR & SALIVATION & LACRIMATION : 

18 SCORING FOR TREMOR & SALIVATION & LACRIMATION

EVALUATION : 

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. 19 EVALUATION

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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. 20

MPTP Model For PD : 

PURPOSE AND RATIONALE MPTP (N-methyl-4-phenyl-1,2,3,tetrahydropyridine) has been shown to cause symptoms of Parkinson’s disease in exposed individuals. 21 MPTP Model For PD

PROCEDURE : 

22 PROCEDURE

EVALUATION : 

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). 23 EVALUATION

RESERPINE ANTAGONISM : 

PURPOSE AND RATIONALE: Reserpine induces depletion of central Acetylcholine stores. 24 RESERPINE ANTAGONISM

PROCEDURE : 

25 PROCEDURE

EVALUATION : 

Locomotor activity and grooming scores of drug treated animals are compared with controls treated with reserpine and vehicle only by analysis of variance. 26 EVALUATION

REFERENCE : 

Goodman & Gilmon’s, The Pharmacological Basis Of Therapeutics. By Laurence L. Brunton, John S. Lazo. Keith L. Parker, 11th edition, Page no:-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 No : 416. 27 REFERENCE

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28 Rang H.P., Dale M.M., Pitter J.M,Flower R.J.(Pharmacology). Elsevier India Pvt Ltd. 6th Edition: Harsh Mohan, Fifth Edition, “Textbook Of Pathology” Jaypee Brothers Medical Publisher (P)LTD, Page No: 910-911 http://www.holisticonline.com/remedies/parkinson/pd_what-is.htm http://www.emedicinehealth.com/parkinson_disease/article_em.htm http://www.parkinsonindia.org/

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