Central Nervous System Depressants 13 Central Nervous System Depressants Medicinal Chemistry Dr.Narmin Hussen Lecture 1

CNS depressants CNS depressants are drugs that can be used to slow down or “depress” the functions of the CNS. CNS depressants can be classified into: Sedative–hypnotics. Antipsychotics.

Anxiolytic, Sedative, And Hypnotic Agents Sedatives are drugs used to induce a mild state of CNS depression characterized by both mental and physical calmness. Hypnotics are drugs used to induce and maintain sleep. Dose: ↑ Sedation ► Hypnosis ► Surgical anesthesia.

Sedative, And Hypnotic Agents 1- GABAA receptor modulators Benzodiazepines Barbiturates Nonbenzodiazepine hypnotics 2- Melatonin-1 receptor (MT1) agonists. 3- Miscellaneous drugs such as chloral hydrate

GABAA Receptors

Benzodiazepines and related compounds can act as agonists, antagonists, or inverse agonists at the benzodiazepine-binding site on GABAA receptor. Beta-carboline and benzodiazepine interactions with GABAA receptor-gated chloride channels Flumazenil is useful in reversing the sedation and respiratory depression that often occur when benzodiazepines β–carbolines are negative modulators (inverse agonists) at benzodiazepine modulatory sites Negative modulators diminish the positive effect of GABA on chloride flux.

Benzodiazepines Drugs

Benzodiazepines

Triazolobenzodiazepines Drugs

Nonbenzodiazepine Bzras:

Melatonin Receptor Agonist: Melatonin is increase or decrease by? Ramelton metabolism?

Barbiturates Structure–Activity Relationships of Barbiturates

Pharmacokinetic of barbiturates:

Barbiturates with a Long Duration of Action (More Than 6 Hours): Barbiturates with an Intermediate Duration of Action (3–6 Hours):

Barbiturates with a Short Duration of Action (Less Than 3 Hours):

Miscellaneous Sedative–Hypnotics: A wide range of chemical structures (e.g., imides, amides, alcohols) can produce sedation and hypnosis resembling those produced by the barbiturates. 1-Amides and Imides: 2-Alcohols and Their Carbamate Derivatives:

3-Aldehydes and Their Derivatives: Chloral hydrate In Alkaline and hydroalcoholic solutions? Weak acid or weak base?

Questions What is the role of Log P on brain penetration? Explain which drugs highly brain penetrated according to different logP range? Which benzodiazepines shown below is/are short acting?