Drugs Acting on CNS Dr. Amged 1 Depressant Drugs Dr. Amged 2 Antipsychotic Drugs Dr. Amged 3 • An antipsychotic (or major tranquilizer or neuroleptic) is a medication primarily used to manage psychosis (e.g., delusion or hallucination), particularly in schizophrenia and bipolar disorder. Dr. Amged 4 • Psychoses can be organic or related to a specific toxic chemical, or to a definite disease process, or they can be idiopathic. • Idiopathic acute psychotic reactions have been reported to follow extremely severe acute stress. • Schizophrenia is a group of chronic idiopathic psychotic disorders. Dr. Amged 5 • Suppression of the dopamine activity is the major mechanism by which the antipsychotics elicit their action (mesolimbic pathway). • This may be achieved via direct interaction (antagonism) with D2 receptors. • Other CNS receptors systems (acetylcholine, histamine, norepinephrine, and serotonin) appear to be involved, especially for the atypical drugs. Dr. Amged 6 Classification of Antipsychotic Agents • Phenothiazine and thioxanthene derivatives. • Butyrophenone derivatives. • Benzamide derivatives. • Benzazepine derivatives. • Benzisoxazole and benzisothiazole derivatives. Dr. Amged 7 Development of Phenothiazines and Thioxanthenes Dr. Amged 8 Development of Phenothiazines and Thioxanthenes Dr. Amged 9 Dr. Amged 10 Structure-Activity Relationships Dr. Amged 11 Structure-Activity Relationships Dr. Amged 12 Structure-Activity Relationships Dr. Amged 13 Structure-Activity Relationships Dr. Amged 14 Structure-Activity Relationships Dr. Amged 15 Structure-Activity Relationships Dr. Amged 16 Structure-Activity Relationships • Long duration! Dr. Amged 17 Metabolism of Chlorpromazine • More than 30 metabolites! Dr. Amged 18 Synthesis of Chlorpromazine Dr. Amged 19 Development of Butyrophenone Neuroleptics Dr. Amged 20 Development of Butyrophenone Neuroleptics Dr. Amged 21 Dr. Amged 22 Dr. Amged 23 Structure-Activity Relationships Dr. Amged 24 Structure-Activity Relationships Dr. Amged 25 Structure-Activity Relationships Dr. Amged 26 Structure-Activity Relationships Dr. Amged 27 Structure-Activity Relationships Dr. Amged 28 Structure-Activity Relationships Dr. Amged 29 Structure-Activity Relationships Dr. Amged 30 Structure-Activity Relationships Dr. Amged 31 Structure-Activity Relationships Dr. Amged 32 Structure-Activity Relationships Dr. Amged 33 Dr. Amged 34 Metabolism of Haloperidol Dr. Amged 35 Benzamide Derivatives • Local anesthetic & antiemetic properties. • Neuroleptic properties & Anticholinesterase properties. • Blockade of D2/D3, M3, 5-HT1A, 5-HT3. Dr. Amged 37 Benzamide Derivatives • Local anesthetic & antiemetic properties. • Neuroleptic properties & Anticholinesterase properties. • Blockade of D2/D3, M3, 5-HT1A, 5-HT3. Dr. Amged 38 Dr. Amged 39 Dr. Amged 40 Dr. Amged 41 Dr. Amged 42 Benzazepine Derivatives Dr. Amged 43 Benzisoxazole & Benzisothiazole Derivatives Dr. Amged 44.