Pharmacology of

Central Nervous
System Drugs

 Gestina Aliska, MD, ClinPharm

 Pharmacology and Therapeutics
Department
 Faculty of Medicine, Andalas University
Outlines
Classification
Definitions
Neurotransmitters
Drugs acting on CNS
CNS depressants
CNS stimulants
Miscellaneous
 Drugs acting on CNS
Sedatives …. Diazepam, Oxagepam etc.
Mainly two groups: Hypnotics …. Clobazepam, Nitrazepam etc.
CNS depressants Narcotics …. Morphine, Codeine etc.
CNS stimulants
(Neuraleptics) GA ….. Barbiturates, Halothane etc.

Directly acting on CNS Reflexly acting on CNS

Caffeine, Aminophylline,
Cortical …. Amphetamine, Ephedrine etc. (Nicotine, Lobetine etc.)

Medullary …. Picrotoxin, Adrenaline, Nikethamide etc.

Spinal …. Strychnine, Brucine etc.

 Structural &
Functional Unit
Neurons: of NS (10
billion neurons
in brain)

• Chemical substances
• Carry messages from
Neuro- one neuron to another
transmitters: • or from a neuron to
body tissues e.g. Sk.
muscles
A Neuron
Synapse:
Small gap separating neurons

Receptors:
 Macro-molecules
 Lipoprotein in nature
Axon terminal of
 Situated on or inside the cell Presynaptic neuron
membrane
Synapse
 Having recognition properties Dendrite of
Postsynaptic neuron

Fig: Synapse
 Process of Typical Synaptic Connection
Presynaptic membrane or element

Action Potential

Activates Ca++ ion Channel Ca2+

Channel
Neurotransmitters Exocytosis of
neurotransmitters

+++AP+++ Na+
Released in Synaptic Cleft
K+

Post synaptic membrane

(receptors or ion channels)

Exert action
ION CHANNELS &
NEUROTRANSMITTER RECEPTORS
 Themembranes of nerve cells contain two types of
channels defined on the basis of the mechanisms
controlling their gating (opening and closing): voltage-
gated and ligand-gated channels.
Sites of drug action
Summary of
neurotransmitter
pharmacology in
the central
nervous system
Summary of
neurotransmitter
pharmacology in
the central
nervous system
 Neurotransmitters in CNS
I. Amino acids : Ach, GABA, Glutamate, Glycine
II. Monoamines : NE, Dopamine, Serotonin
III. Peptides : Opioid peptides, Neurotensin, Substance P,
Somatostatin, Neuropeptide Y
IV. Nitric oxide
V. Endocannabinoids
VI. Histamine
VII. Tachykinins
Drugs acting on CNS
CNS Depressants: Anxiolytics and Sedative-Hypnotics
Sedatives (anxiolytic): Hypnotics:
 Anxiolytic drug  Depress CNS to
 Reduce anxiety, excitement, the point that they
nervousness, irritability cause normal
sleep
 Exert calming effect
 Mild depression of CNS
 Don’t cause sleep
 Little or no effect on motor or
mental functions
CNS Depressants: Anxiolytics and Sedative-Hypnotics
Progressive

}
Non Benzodiazepine

{ Sedative-Hypnotic drugs Depression of CNS

Sedation
Dose dependent

Higher
Hypnosis
Lower

Dose
Dose

depression of CNS
Narcosis

Coma

Sedatives Hypnotics GA
Death
Classification: Sedatives-Hypnotics
 Sedatives-Hypnotics: Benzodiazepines

Clinical uses of sedative-hypnotics

 Mechanism of Action of Benzodiazepines

Benzodiazepines
Binds with specific regulatory
site on GABA receptor in brain
Opening of Cl- channels
(Enhancement of Cl-
conductance)

Hyperpolarization of cells
Enhance GABA activity

Depression of CNS
 Pharmacological action: Benzodiazepines

CNS effects:

•Sedation
•Hypnotic (induction of sleep)
•Muscle relaxant
•Anticonvulsant
•Anesthesia
•Effects on respiration and
cardiovascular function
Pharmacokinetics of benzodiazepines
and newer hypnotics
 Adverse effects : Benzodiazepines
Adverse effects
a)Normal dose:
Dry mouth
Light headache
Confusion
Ataxia

Impair driving skill
b)Acute overdose: Prolong sleep
c) Tolerance & dependency
Choice
The use of sedative-hypnotics
for more than 1-2 weeks leads
to some tolerance to their
effects on sleep patterns.

d)Decrease libido
 Sedatives-Hypnotics: Barbiturates
Classification
Malonic acid Ultra-short acting • Acts within seconds, DOA: 30 mins
(e.g. Thiopental-Na) • Main use: IV anaesthetic

Short acting • DOA: 2 hours

Barbituric (e.g. Pentobarbital) • Main use: Sedative
acid
Intermediate acting • DOA: 3-5 hours
(e.g. Amobarbital) • Main use: Hypnotic

Barbiturates Long acting DOA: > 6 hours

(Phenobarbitone) Main use: Anticonvulsant
 Mechanism of Action Barbiturates
Barbiturates + GABAA receptor
Barbiturates + AMPA receptor

Activation of GABA receptor

Inhibition of AMPA receptor
Opening of Cl- Channel
Inhibition of Glutamate duration of GABA gated channels opening

Hyperpolarization of cells

Depression
of CNS Potentiate GABA inhibitory action
 Barbiturates: Indications & Adverse effects

Indications Adverse effects

Anticonvulsants Drowsiness
Over excitement
Sedative & Hypnotics
Night mares & night terrors
IV anesthesia Weakness Allergic skin
Hyperbilirubinemia reaction Localized or
diffuse pain Psychologic
Kernicterous
dependence Tolerance
Cholestasis
 Sedatives-Hypnotics: Newer drugs
Anxiety & Sleep Disorder

Buspirone &
analogs (ipsapirone, Zolpidem Zaleplon
gepirone,
tandospirone)
 CNS Depressants: Tranquilizers

 Produce calmness & quietness

 Reduce anxiety, tension & aggression
 Also called “PEACE PILL”

Example:
Major: Phenothiazine derivatives (Chlorpromazine,
Promethazine etc.), Reserpine etc.
Minor: Benzodiazepines, Phenobarbitone etc
CNS Depressants: Anticonvulsant Drugs

Examples
carbamazepine (Epitol,
Used to treat Tegretol)
epileptic seizures
clonazepam (Klonopin)

diazepam (Valium)
More accurately
called antiepileptic divalproex (Depakote)
drugs
phenytoin (Dilantin)
 Anticonvulsant Drugs: MOA

Blocking of Na+
channels
Principle:

Enhance GABA
Depolarization of nerve:
Convulsion mediated synaptic
inhibition
Repolarization of nerve:
Returning to normal state Ca2+ channel
blockade
 Analgesics

Narcotic

Relieve pain

Don’t impair degree

of consciousness
Non-Narcotic
 Narcotic VS Non-narcotic analgesic

Narcotic Non-narcotic
Opioid
Highly potent Less potent
Antagonists…
e.g. Naloxane
Addicting Less-addicting

Depress CNS Don’t depress

Addicting Drugs ….
No AI & AP Have AI & AP e.g. Morphine, Heroin
action action

Low TI High TI
 Opioids: Actions & MOA (General)
Actions MOA
Analgesia Respiratory Stimulation of opioid receptors:
depression mu(µ), delta(δ), kappa(ƙ)
Constipation
Increase K+ efflux, Reduce Ca+
Urinary Retention influx, Decrease cAMP
Cough suppression
Emesis Inhibition of cell firing
Miosis
Sedation
Elimination of pain
Euphoria/ Dysphoria
 CNS Stimulants
Directly acting on CNS: Progressive Grade of CNS
excitation
i. Cortical stimulants (Amphetami ne,
Mild hyper-
Aminophylline) excitability
ii. Medullary stimulants (Picrotoxin,
Severe hyper-
Nikethamide) excitability
iii. Spinal stimulants (Strychnine, Brucine)
Mild convulsion
Reflexly acting on CNS:
Nicotine, Ammonia etc. Severe
convulsion
 Miscellaneous
Levodopa,
Parkinsonism
Amantadine etc.
Baclofen,
Multiple Sklerosis
Tizanidine etc.

Alzheimer’s Disease Donepezil,

tacrine etc.

Myasthenia Gravis Azathioprine

Psychotropic
Schizophrenia Drugs
Wassalam
Thank You