Drugs Acting on CNS

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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.

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NIH Public Access Author Manuscript Bioorg Med Chem
NIH Public Access Author Manuscript Bioorg Med Chem. Author manuscript; available in PMC 2013 February 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Bioorg Med Chem. 2012 February 1; 20(3): 1291–1297. doi:10.1016/j.bmc.2011.12.019. Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents Kwakye Pepraha, Xue Y. Zhua, Suresh V. K. Eyunnia, Vincent Setolab, Bryan L. Rothb, and Seth Y. Ablordeppey*,a aDivision of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA bDepartment of Pharmacology, Medicinal Chemistry and Psychiatry, University of North Carolina at Chapel Hill, School of Medicine, NC 27599, USA Abstract Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contributes to changes in binding to the receptors of interest. This strategy has resulted in the identification of several new agents, compounds 16, 18, 19, 23, 24 and 25, with binding profiles which satisfy our stated criteria for agents to act as potential atypical antipsychotics. This research demonstrates that haloperidol can serve as a useful lead in the identification and design of new agents that target multiple receptors
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Name of Medicine
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Zyprexa, INN-Olanzapine
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Dictionary of Contact Allergens: Chemical Structures, Sources And
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Butler. K ...99 Juby. P . F ...208 Kaiser. C ...6. 18
CONTRI BUTORS Bach. M . K ........ 238 Lienhard. G . E ........ 249 Benet. L . Z ....... 259 Morrow. D . F ......... 182 Blohm. T . R ....... 169 Nagasawa. H . T ........ 269 Bundy. G . L ....... 157 Pachter. 1 . J ........ 157 Burgus. R ........ 194 Rachlin. A . I ........ 145 Butler. K ........ 99 Robinson. F . M ........ 31 Cheng. C . C ....... 129 Roe. A . M .......... 59 Colten. H . R ....... 228 Rudzik. A . D ......... 39 Cronin. T . H ....... 119 Sciavolino. F . C ....... 99 Czuba. L . J ....... 78 Schowen. R . L ........ 279 Davies. J ........ 217 Schwender. C . F ....... 69 Drube. C . G ....... 109 Stewart. J . M ........ 289 Engelhardt. E . L ..... 6 Thomas. R . C ......... 296 Friis. W ......... 39 Thompson. J . A ........ 269 Gallo. D ......... 182 Topliss. J . G ........ 59 Gandour. R . D ...... 279 Tozzi. S ........... 89 Harbert. C . A ...... 47 Waitz. J . A ......... 109 Hitchings. G . H ..... 1 Wechter. W . J ........ 217 Hoffer. M ........ 145 Weissman. A ......... 47 Hudyma. T . W ....... 208 Wiley. R . A ......... 259 Juby. P . F ........ 208 Zirkle. C . L ......... 6. 18 Kaiser. C ........6. 18 ANNUAL REPORTS IN MEDICINAL CHEMISTRY Volume 7 Sponsored by the Division of Medicinal Chemistry of the American Chemical Society Editor-in- Chief: RICHARD V. HEINZELMAN THE UPJOHN COMPANY KAUMAZOO, MICHIGAN SECTION EDITORS EDWARD ENGELHARDT 0 JOHN TOPLISS 0 KENNETH BUTLER IRWIN PACHTER 0 WILLIAM WECHTER 0 ROBERT WILEY @ACADEMIC PRESS New York and London 1972 COPYRIGHT 0 1972, BY ACADEMICPRESS, INC. ALL RIGHTS RESERVED NO PART OF THIS BOOK MAY BE REPRODUCED IN ANY FORM, BY PHOTOSTAT, MICROFILM, RETRIEVAL SYSTEM, OR ANY OTHER MEANS, WITHOUT WRITTEN PERMISSION FROM THE PUBLISHERS. ACADEMIC PRESS, INC.
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INDEX Figures and tables are indicated by “f” and “t” following page numbers. AAD. See Antibiotic-associated diarrhea delirium and, 326t morbidity and mortality for, 956 AAN (American Academy of Neurology), 264–265 hirsutism and, 194, 195t, 199t overview, 955 Abacavir neutropenia/agranulocytosis and, 1089t patient education on, 957 acidosis and, 1003t ototoxicity and, 1234t prevention of, 956–957 allergic and hypersensitivity reactions to, 75t, peripheral neuropathy and, 281t risk factors for, 956 88, 112 photosensitivity and, 144t Acute kidney injury (AKI), 941–960 anxiety and, 400t, 403 tardive dyskinesia and, 265 acute interstitial nephritis, 955–957 cutaneous diseases and, 111t, 113t taste disorders and, 1259t, 1261t acute tubular necrosis, 949–955 genetic variability and, 16t visual disturbances and, 296t community-acquired, 941–942, 944 genetic variations affecting, 36t Acetohydroxamic acid, 1066t, 1070t defined, 941 glucose/insulin dysregulation and, 690 Acetylcholine glomerulonephritis, 958–960 human leukocyte antigen and, 37, 38 cognitive disorders and, 359, 360 hemodynamic-mediated, 942–949 malignant hyperthermia and, 1186 delirium and, 329 hospital-acquired, 941–942 myocardial ischemia/acute coronary syndromes myocardial ischemia/acute coronary syndromes nephrolithiasis, 957–958 and, 472t and, 473t Acute lymphoblastic leukemia (ALL), 1283, 1286, nausea/vomiting and, 909t myopathy and, 1153 1291 neutropenia/agranulocytosis and, 1089t psychosis and, 418 Acute myeloid leukemia (AML), 1283–1287, oral erythema multiforme and, 1266t sexual dysfunction and, 766 1289–1292 osteoporosis/osteomalacia and, 1127 in sleep cycles, 349 Acute tubular necrosis (ATN), 949–955 ototoxicity and, 1234t Acetylcholinesterase inhibitors, 335 causative agents of, 943t, 949–950 pharmacogenomic tests for, 35 Acetylcysteine, 440, 1243 clinical presentation of, 946t, 951 Abatacept, 1270t Acetyl-L-carnitine, 286, 287t, 288 differential diagnosis of, 951 Abciximab, 238t, 239, 1029t, 1050t, 1052t, 1053 Acetylsalicylic acid.
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