Drugs acting on Central Nervous System

Sedatives and Hypnotics

The reticular activating
system (RAS) participates in
fight-or-flight responses.
Motor tension -a state of
muscle tension in which the
individual is restless and tires
easily.
Click to add text
 Chlordiazepoxide

7-chloro-4-hydroxy-5-phenyl-3H-1,4-benzodiazepin-2-methyl
imine

Chlordiazepoxide is a long-acting benzodiazepine with anxiolytic, sedative and hypnotic activity.

Chlordiazepoxide exerts its effect by binding to the benzodiazepine site at the gamma-aminobutyric acid (
GABA) receptor-chloride ionophore complex in the central nervous system (CNS). This leads to an increase in
the opening of chloride channels, membrane hyperpolarization and increases the inhibitory effect of GABA on
the CNS.
7-chloro-1-methyl-5-phenyl-3H-
1,4-benzodiazepin-2-one
Oxazepam

7-chloro-3-hydroxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one

Oxazepam is a synthetic benzodiazepine derivative with anxiolytic and sedative hypnotic

properties. Although the mechanism of action has not been fully elucidated, oxazepam appears to
enhance gamma-aminobutyric acid (GABA) receptor affinity for GABA, thereby prolonging
synaptic actions of GABA.
 Chlorazepate

7-chloro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepine-3-carboxylic acid

Clorazepate is a benzodiazepine used as an anticonvulsant as adjunctive therapy in management of

epilepsy and as an anxiolytic for therapy of anxiety and alcohol withdrawal. Therapy with clorazepate is
not associated with serum aminotransferase elevations, and cases of clinically apparent liver injury from
clorazepate have been reported but are very rare.
7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-
dihydro-1,4-benzodiazepin-2-one
 Alprazolam

8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine

Alprazolam is a triazolobenzodiazepine agent with anxiolytic, sedative-hypnotic and anticonvulsant activities.

Alprazolam binds to a specific site distinct from the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)
binding site on the benzodiazepine-GABA-A-chloride ionophore receptor complex located in the limbic, thalamic
and hypothalamic regions of the central nervous system (CNS). This binding causes an allosteric modification of
the receptor and enhances the affinity of GABA to the receptor leading to an increase in the frequency of 
chloride-channel opening events. This leads to an increase in chloride ion conductance, neuronal
hyperpolarization, inhibition of the action potential and leads to a decrease in neuronal excitability.
 Zolpidem

N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide

Zolpidem is a benzodiazepine receptor agonist that is used for the treatment of insomnia. Zolpidem has
rarely been implicated in causing serum enzyme elevations and has not been reported to cause clinically
apparent liver injury.
Barbital

5,5-diethylpyrimidine-2,4,6(1H,3H)-trione

Barbital (or barbitone), marketed under the brand names Veronal for the pure acid and Medinal for the
sodium salt, was the first commercially available barbiturate. It was used as a sleeping aid (hypnotic)
from 1903 until the mid-1950s.
 Synthesis of Barbital

Urea Diethyl malonate Barbital

Barbital was prepared by condensing diethylmalonic ester with urea in the presence of sodium ethoxide.

5-ethyl-5-phenyl-1,3-diazinane-2,4,6-trione
Synthesis of Phenobarbital
 Mephobarbital

5-ethyl-1-methyl-5-phenyl-1,3-diazinane-2,4,6-trione

Mephobarbital, 5-Ethyl-1-methyl-5-phenylbarbituric acid, is a babiturate with sedative, hypnotic, and

anticonvulsant properties. It occurs as a white, nearly odorless, tasteless powder and is slightly soluble in
water and in alcohol.
 Amobarbital

5-ethyl-5-(3-methylbutyl)-1,3-diazinane-2,4,6-trione

Amobarbital (formerly known as amylobarbitone or sodium amytal as the soluble sodium salt) is a drug that is a 
barbiturate derivative. It has sedative-hypnotic properties. It is a white crystalline powder with no odor and a
slightly bitter taste. It was first synthesized in Germany in 1923. It is considered an intermediate acting barbiturate.
 Butabarbital

5-butan-2-yl-5-ethyl-1,3-diazinane-2,4,6-trione

Butabarbital, or Butisol, is a fast onset barbiturate with short duration of action compared to other barbiturates. This
makes butabarbital a useful drug for treating severe insomnia and pre-operative anxiety. Butabarbital is less
commonly used in recent years, as more patients are typically prescribed benzodiazepines.
 Secobarbital

5-pentan-2-yl-5-prop-2-enyl-1,3-diazinane-2,4,6-trione

Secobarbital (marketed by Eli Lilly and Company under the brand names Seconal and Tuinal) is a barbiturate
derivative drug with anaesthetic, anticonvulsant, sedative and hypnotic properties. It is commonly known as
quinalbarbitone in the United Kingdom.
Miscellaneous Agents – Amides and imides

3-ethyl-3-phenylpiperidine-2,6-dione
 Miscellaneous Agents – Alcohol and their carbamate derivatives

1. Meprobomate

[2-(carbamoyloxymethyl)-2-methylpentyl] carbamate

Meprobamate is a carbamate derivate with hypnotic, anti-anxiety, sedative, anticonvulsant and some indirect
muscle relaxant properties. Meprobamate is a sedative used for anxiety and insomnia first made available in the
1950s when it became very popular, but which is now rarely used. Meprobamate therapy was not associated with
liver enzyme elevations and has not been linked to instances of clinically apparent liver injury.
 2. Ethchlorvynol

(E)-1-chloro-3-ethylpent-1-en-3-ol

Ethchlorvynol is propargyl alcohol in which the methylene hydrogens are substituted by ethyl and 2-
chlorovinyl groups. A hypnotic and sedative, it is used for treatment of insomnia in some cases where an
intolerance or allergy to more commonly used drugs exists. It has a role as a sedative. It is a tertiary alcohol, an
organochlorine compound, an enyne and a terminal acetylenic compound.
Miscellaneous Agents – Aldehydes and their derivatives

2,4,6-trimethyl-1,3,5-trioxane

Paraldehyde is a trioxane that is

1,3,5-trioxane substituted by
methyl groups at positions 2, 4 and
6. It has a role as a sedative.
 2. Triclofos sodium

sodium;2,2,2-trichloroethyl hydrogen phosphate

Triclofos is a prodrug which is metabolised in the liver into the active drug trichloroethanol. The half-life
of triclofos is fairly long and it may cause drowsiness the next day. Trichloroethanol may cause liver
damage and triclofos should not be used for extended periods.