1. PHL. 322 Final lab Presented by Mohammed Alyami Teaching assistant Department of pharmacology & Toxicology College of pharmacy KSU

2. Antipsychotic drugs Antischizophrenia drugs Neuroleptic drugs Major tranquilizers Used to treat schizophrenia Used to treat schizophrenia

3. 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.

4. 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

5. They reduce dopaminergic neurotransmission

6.  Mesolimbic pathway  Mesocortical pathway We will discuss only two pathways

7. 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.

8. They reduce dopaminergic neurotransmission

9. 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

10. D 2 receptor Loose binding Atypical - Dopamine

11. 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?

12. 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

13. 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

14. 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

15. 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)

16. 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

17. 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)

18. Conclusion : - Control AP Active time 240 sec 120 sec 180 sec 60 sec depression