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PHL. 322 Final lab Presented by Mohammed Alyami Teaching assistant Department of pharmacology & Toxicology College of pharmacy KSU
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Antipsychotic drugs Antischizophrenia drugs Neuroleptic drugs Major tranquilizers Used to treat schizophrenia Used to treat schizophrenia
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Describe the fragmented thinking of people with the disorder Split Mind Is a serious brain illness which are characterized by severe problems with a person’s -thoughts, -feelings, - behavior, - and use of words and language. Is a serious brain illness which are characterized by severe problems with a person’s -thoughts, -feelings, - behavior, - and use of words and language.
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Neuroleptic drugs Typical (classic drug) Phenothiazines class Chlorpromazine Thioridazine Fluphenazine Thioxanthenes class Thiothixene Butyrophenones class Haloperidol Atypical (newer agent) Heterocyclic structure Clozapine Olanzapine Quetiapine Risperidone Ziprasidone
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They reduce dopaminergic neurotransmission
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Mesolimbic pathway Mesocortical pathway We will discuss only two pathways
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Mesolimbic pathway Excess activity implicated in: -Positive symptom schizophrenia e.g. - hallucinations - delusions Mesocortical pathway Diminished activity implicated in : -Negative symptoms of schizophrenia e.g. Restrictions in -emotion, -thought, -speech, -pleasure and attention.
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They reduce dopaminergic neurotransmission
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D 2 receptor Typical - Atypical - 5-HT 2A receptor Atypical - Typical is D 2 antagonistAtypical is serotonin-dopamine antagonist high affinity to D 2 high affinity to 5-HT 2A Low affinity to D 2 Binding to D 2 receptor (tight) Binding to D 2 receptor (loose) Atypical dissociate rapidly from D 2 receptor
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D 2 receptor Loose binding Atypical - Dopamine
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High occupancy for D 2 D 2 occupancy 78% 75% 60% Antipsychotic efficacy EPS High EPS risk Which has more EPS risk typical or atypical neuroleptic? And Why?
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Atypical neurolepticTypical neuroleptic 5-HT 2A antagonist D 2 antagonist Rapid D 2 Dissociate D 2 antagonistMOA Antagonism of H1, M1, 5-HT 2c, alpha 1 receptor, among other Antagonism of H1, M1, alpha-1 receptor, among other Other effect Summary
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The Swimming Test (Behavioral despair test ) Shows promising potential as a screening for novel Antidepressants May be to understand pathophysiology of depression Depression Characterized by A lack of motivationIncrease despair Increase immobility decrease mobility
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Procedure 1- mouse is placed in acrylic glass cylinders filled with water (23–25 °C) to a depth of 17 cm (can reach to 20 cm ). 2- The water level in the glasses must be - high enough to prevent the mouse from touching the bottom of the cylinder with his paws or tail, - low enough to avoid an escape through the top opening of the cylinder. 17cm
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The Swimming Test Control mouse Depression mouse (model ) Mouse with Antipsychotic Rapid despairResistant despair Three groups of mice Long Active swimming time (increased mobility ) low Active swimming time (increased immobility)
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3 - A 6-minute session was employed (control mouse), and mobility time was scored only during the final 4 minutes, to eliminate the period of escape activity. Active
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Duration of the experiment = 6 minutes 2 minutes The last 4 minutes is counted Zero time Neglected -We Record the time(each minute) which is the mouse is active and - Stop the time when it is non-active (immobility= passive floating, or making only movements necessary to remain afloat)
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Conclusion : - Control AP Active time 240 sec 120 sec 180 sec 60 sec depression
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