Medicinal Chemistry 5 Flashcards
What are sedative-hypnotics?
Drugs used to slow down mental and physical functions of the body (CNS depressant)
What is the primary difference between sedatives and hypnotics?
Sedatives produce mild depression and calm anxiety without causing drowsiness; hypnotics induce sleep when natural sleep is impossible.
What is the ideal characteristic of a hypnotic drug?
Induces sleep similar to natural sleep.
Name the common groups of sedative-hypnotics currently used.
- Alcohols
- Barbiturates
- Benzodiazepines
- Imidazopyridines
- Cyclopyrolones
- Pyrazolopyrimidines
- Melatonin receptor agonists
What are some potential hazards associated with the use of ethanol as a sedative?
Production of alcoholism and toxic effects on many organ systems.
How does the hypnotic activity of alcohols change with the length of the carbon chain?
Hypnotic activity increases as the length of the carbon chain increases up to 8 carbons.
What is chloral hydrate’s status in modern medicine?
No longer used as a sedative-hypnotic due to toxicity.
What is the active metabolite of chloral hydrate?
Trichloroethanol
What is the mode of action of barbiturates?
Enhance GABA binding, prolong mean opening time of chloride channels, leading to CNS depressant effects.
Why are barbiturates largely replaced by benzodiazepines?
Due to their safety profile; barbiturates cause tolerance, dependence, and overdose risks.
What is the significance of the carbonyl group in benzodiazepines?
Necessary for optimal activity, interacting with a receptor histidine residue.
How do benzodiazepines enhance GABA’s effect?
By binding and stimulating specific benzodiazepine receptors adjacent to GABAA receptors.
What are the key structural requirements for benzodiazepines?
- N atom is essential for activity
- NH optimal for receptor affinity
- Carbonyl group at 2-position is crucial
What happens when the 4,5 double bond in benzodiazepines is saturated?
It decreases activity.
What are the effects of alkyl substitution at the 3-position of benzodiazepines?
Decreases activity; substitution with hydroxyl is tolerated.
How does the presence of electron-withdrawing groups at position 7 affect benzodiazepine activity?
Promotes activity.
What is the role of the phenyl group at position 5 in benzodiazepines?
Very important for activity; ortho or di-ortho substitution increases activity.
What is the significance of the 2’-chloro substitution in lorazepam?
Increases activity.
What is flurazepam primarily used for?
As a hypnotic and anxiolytic.
What unique metabolic characteristic does flurazepam have?
Metabolized to 2’-fluoronordiazepam, which has its own hypnotic and antianxiety activities.
What is the classification of barbiturates based on their duration of action?
- Short-acting
- Intermediate-acting
- Long-acting
True or False: Benzodiazepines do not require a nitrogen atom for activity.
False
Fill in the blank: The most important inhibitory transmitter of the mammalian CNS is _______.
γ-Aminobutyric acid (GABA)
What is the primary method of metabolism for benzodiazepines?
Hydroxylation of the methyl substituent on the triazolo or imidazolo ring.
