Unit 4: Drugs Acting on Central Nervous System (Part I)

Semester 4

BP402T

Introduction to Drugs Acting on Central Nervous System (Part I)

Central Nervous System (CNS) drugs have profound effects on human mood, consciousness, and behavior. This unit covers the medicinal chemistry of the classic depressants used for anxiety and insomnia: Sedatives and Hypnotics, including the detailed SAR of Benzodiazepines and Barbiturates. It progresses to Antipsychotics (neuroleptics) used for schizophrenia, focusing on Phenothiazines and Butyrophenones. Lastly, it covers Anticonvulsants (AEDs) used in the chemical management of epilepsy. Syntheses of Diazepam, Chlorpromazine, and Phenytoin are critical.

Syllabus & Topics

1Sedatives and Hypnotics: Benzodiazepines (SAR, Diazepam, Lorazepam, Alprazolam).
2Sedatives and Hypnotics: Barbiturates (SAR, Barbital, Phenobarbital, Pentobarbital).
3Miscellaneous sedatives: Amides, Imides, Alcohols (Glutethimide, Meprobamate).
4Antipsychotics: Phenothiazines (SAR, Chlorpromazine, Trifluoperazine).
5Antipsychotics: Fluorobutyrophenones (Haloperidol) and Atypical antipsychotics.
6Anticonvulsants: Hydantoins (Phenytoin), Barbiturates, Oxazolidinediones.
7Synthesis of Diazepam, Chlorpromazine hydrochloride, and Phenytoin.

Learning Objectives

Describe the structural features necessary for Benzodiazepine anxiolytic activity.

Understand how carbon chain length in Phenothiazines switches activity from antihistaminic to antipsychotic.

Detail the molecular mechanics and syntheses of key CNS depressants.

Classify anticonvulsants chemically and map their structural similarities.

Frequently Asked Questions (FAQs)

Q1. What is the Structural Nucleus of a Benzodiazepine?

Benzodiazepines contain the 1,4-benzodiazepine ring system, which consists of a benzene ring fused to a seven-membered diazepine ring. An electronegative substituent such as chlorine or nitro at position 7 is essential for strong sedative-hypnotic activity, and the presence of a phenyl ring at position 5 significantly enhances activity.

Q2. How Do Barbiturates Cause Their Sleeping Effect?

Barbiturates are central nervous system depressants derived from barbituric acid. They act on the GABAA receptor and increase the duration of chloride channel opening, leading to neuronal hyperpolarization and suppression of brain activity, thereby producing sedation and sleep.

Q3. What is the SAR of Phenothiazine Antipsychotics?

Phenothiazine antipsychotics require a three-carbon alkyl chain linking the N10 position of the phenothiazine nucleus to a terminal aliphatic amino group. A two-carbon chain shifts activity toward antihistaminic effects rather than antipsychotic action. An electron-withdrawing group at position 2, such as chlorine in Chlorpromazine, is crucial for optimal binding to the dopamine D2 receptor.

Q4. How Does Phenytoin Control Seizures Without Severe Sedation?

Phenytoin is a hydantoin derivative that stabilizes the inactivated state of voltage-gated sodium channels in neurons. This prevents high-frequency repetitive neuronal firing associated with seizures, without producing the generalized CNS depression seen with barbiturates.