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Drugs Acting on CNS
Dr. Amged 1
Depressant Drugs
Dr. Amged 2
Sedatives & Hypnotics
Dr. Amged 3
Sedative & Hypnotics
• A Sedative drug is a CNS depressant that
decreases excitability but does not induce
sleep.
• A hypnotic drug is a CNS depressant that
produces sleep; used to induce sleep when
natural sleep is impossible.
• Both are referred to as sleeping bills and used
to treat insomnia.
Dr. Amged 4
• Insomnia can be classified as:
- Primary (pathogenesis unknown).
- Secondary (situational stress, lifestyle habits,
drugs, and psychiatric or medical disorders).
Dr. Amged 5
Sleep Cycle
• Wakefulness.
• Nonrapid eye movement [NREM] sleep.
• Rapid eye movement [REM] sleep.
Dr. Amged 6
Sleep Factors
• Many autonomic, physiologic, and
biochemical changes are associated with
wakefulness, NREM sleep, REM sleep, and
circadian rhythmicity.
• Neurotransmitters: catecholamines, serotonin,
histamine, acetylcholine, adenosine, γ-
aminobutyric acid.
• Hormones: growth hormone, prolactin, and
melatonin.
Dr. Amged 7
Sedative-Hypnotic Drugs
• Chloral hydrate.
• Barbiturates.
• Benzodiazepines.
• Nonbenzodiazepines
• Melatonin receptor agonists.
• Antihistamines.
• Antidepressants.
Dr. Amged 8
The ideal sedative-hypnotic should:
• Cause transient decrease in the level of
consciousness for the purpose of sleep without
lingering effects (sleep induction and sleep
maintenance).
• Have no potential for decreasing or arresting
respirations (even at relatively high doses).
• Produce no abuse, addiction, tolerance or
dependence.
Dr. Amged 9
Chloral Hydrate
• It was introduced as a sedative in 1869. During
the 1950s and 1960s, chloral hydrate was
widely promoted as a hypnotic.
• Today, it still finds use as a sedative in
nonoperating room procedures for pediatric
patients.Dr. Amged 10
• Chloral hydrate is a weak acid (pKa = 10.04).
• Quite irritating to mucous membranes, such as
in the stomach.
• Readily absorbed form GIT.
Dr. Amged 11
Dr. Amged 12
Barbiturates
• Cyclic ureides are formed when a dicarboxylic
acid reacts with urea.
Dr. Amged 13
• The cyclic ureides are acidic owing to
enolization.
Dr. Amged 14
• Cyclic ureides derived from malonic acid or
malonic esters are known as barbiturates
because of their relationship of barbituric acid
(malonyl urea).Dr. Amged 15
Dr. Amged 16
• Barbituric acid itself does not possess any
hypnotic properties, but such characteristic is
conferred only when the hydrogen atoms at C-
5 are replaced by organic groups (alkyl or aryl)
Dr. Amged 17
Dr. Amged 18
Dr. Amged 19
Classification of Barbiturates
• Long acting (6-8 hours).
• Intermediate acting (2-6 hours).
• Short acting (1-2 hours).
• Ultra-Short acting ( minutes).
Dr. Amged 20
Long Acting Barbiturates
Dr. Amged 21
Intermediate Acting Barbiturates
Dr. Amged 22
Short Acting Barbiturates
Dr. Amged 23
Ultra-Short Acting Barbiturates
Dr. Amged 24
Mechanism of Action of Barbiturates
• The principal mechanism of action of
barbiturates is believed to be their affinity to
GABAA receptors.
• Barbiturates bind to the GABAA receptors at
binding sites distinct from GABAB binding
sites.
• Barbiturates potentiate the effect of GABA at
these receptors.
Dr. Amged 25
Structure Activity Relationships
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Structure Activity Relationships: 5,5-Disubstitution
• Lipophilic groups increase the activity of
barbiturates (to certain limit).
• Polar groups decrease the activity of
barbiturates.
Dr. Amged 27
Structure Activity Relationships: Substitution on Nitrogen
• Monosubstitution increases lipophilicity.
• Disubstitution renders barbiturates inactive.
Dr. Amged 28
Structure Activity Relationships: Modification of Oxygen
• Replacement of C2 oxygen by sulfur increases
lipid solubility.
Dr. Amged 29
Benzodiazepines
Dr. Amged 30
Nonbenzodiazepines (Z compounds)
Dr. Amged 31
Melatonin Receptor Agonists
• Melatonin, at times referred to as the hormone
of darkness, is synthesized in the pineal gland
and normally is secreted during the night.
Dr. Amged 32
Design of Ramelteon
Dr. Amged 33
Design of Ramelteon
Dr. Amged 34
