CNS drugs

2. CONTENTS
 Introduction
 Neurochemical transmission
 Neurotransmitters in Central Nervous System(CNS)
 Drugs act on Central Nervous System(CNS)

3.  Introduction :-
 The nervous system in higher animals can be divided in to
Central nervous system (CNS)
Peripheral nervous system (PNS)
Autonomic nerve fibres Somatic nerve fibres
 Not only concerned with regulation of specialized functions like circulation,
digestion & respiration responsible for the psychic processes such as felling
, attitude , thoughts & memory .
 CNS & PNS are analogous to elaborate system of telegraphy where in
numerous wires & connections in the form of neurons & synapses being
information from internal & external sources .
 The information is received , decoded are made by various centres in CNS
and instructions sent to peripheral tissues to produce responses
Psychic : Change in emotions , thought & attitude
 Somatic : Changes in various types of body movements
Autonomic : Changes in visceral , circulation &
respiration functions

5. Neurochemical transmission in nervous system :
 Mammalian nervous system is almost exclusively through chemical
messenger
 Neurosecretion is a fundamental property of all neurons
 Neurosecretion is a chemical released at nerve terminals those related to
blood circulation Neurohormones.
 E.g. : Hypothalamic hormones released from hypothalamopitutury
circulation
Neurotransmission
 3process Neuromediation
Neuromodulation

6. Neurotransmission :-
 Impulse is transmitted across a synapse between two neurons .
 Neurotransmitters (NT) are released in to synaptic cleft either by stimulation
or inhibit the post synaptic neuron
Certain criteria in order to accept NT:
 Must be present in the neurons & presynaptic nerve endings should have a
discrete rather than uniform pattern of distribution
 Must be released from presynaptic nerve terminal
 Enzymatic mechanisms capable of synthesizing and degraded the substance
should be present with in the neuron
 Local concentration of the substance related to function of neuronal
structure & fluctuations in its concentration
 Blocking agents should produce demonstrable effects by preventing the
access of transmitter

7.  Neuromediation :-
 Implies the elicitation of the post synaptic response to release
neurotransmitter through secondary response
 Such as cAMP , cGMP & inositol phosphate
 Neuromodulation :-
 Less clearly defined process than neuro-transmission
 Occur at pre & post synaptic levels to regulate the release of NTs
 Arise from neurons as well as from non-neuronal cells they are not stored or
released like neurotransmittors
 Act with a longer duration of action & longer latency of action
 E.G: Adenosine , prostaglandins , nitric oxide

8. CNS neurotransmitters
 CNS has both excitatory & inhibitory chemicals transmitters
 They are Amines : Ach , nor adrenaline , dopamine , serotonin , histamine
Amino acids :- L-glutamic acid & aspartic acid , GABA , glycine
Peptides : substance p , cholecystokinin
• GABA &glycine are inhibitory NT where as dopamine is selectively either
stimulatory or inhibitory at different sites
• Many drugs which modify the functions of CNS and affect the
concentration of one or more of them in Central as well as Peripheral
nervous system
• Many of the endogenous peptides are discovered in the brain e.g.
angiotensin , endorphins , vasopressin , endocrine peptides & gut peptides
• They regulate neuronal functions by themselves

10. Gamma amino butyric acid (GABA)
 Major inhibitory amino acid in NT in brain
 Most of the GABA receptors are composed of α,β,γ subunits
 Receptors composed of α & β subunits produce functional GABAA receptor
bind to barbiturates does not to benzodiazepines
 γ assemble with benzodiazepines
 Absence of GABA benzodiazepines have no effect on GABAA
 GABAB is a metabotropic receptor , activates drug baclofen relaxes muscle
relaxant

11. synthesis
 Glutamine Glutamate
GABA
vesicles
Exocytosis
Presynaptic nerve terminal via
GABA transporters & repacked in
vesicle
Glutamine
Decarboxylation
l-glutamic acid
decarboxylase
stored
Released in synaptic cleft
After release

12. Glutamate & Aspartate
 Is a essential amino acid (EAA)
 These are A.A are present in various parts of brain
 Plays an important role excitatory in NT throughout CNS
 Released from presynaptic nerve terminals & binds to several glutamate
receptors
 Their activation increases the conductance of Na⁺ & Ca⁺⁺ in to cells leading
to depolarization (inotropic glutamate receptors) or stimulates
(metabotropic glutamate receptors)
 2 Inotropic glutamate receptors are NMDA (n-methyl D-aspartic acid) &
non-NMDA (a-amino-3-hydroxy-5-methyl-4-isooxasole propionic acid)
 Non-NMDA associated with excitatory postsynaptic potentials at
glutamatergic synapsis
 NMDA is associated with LTP prolonged increase in size of post synaptic
response to a presynaptic stimulus
 EAA involved in brain process such as learning ,memory, thinking
 Very high concentrations of glutamine can cause neuronal cell death

14. Dopamine and its receptors
 Dopamine is primarily an inhibitory neurotransmitter. Its deficiency causes
extrapyramidal disturbances. There are five receptors identified – D1-D5.
Activation of D1 and D5 stimulate adenylyl cyclase and increase the release
of cAMP;
 D2-4 inhibits adenylyl cyclase and decrease the release of cAMP. The
locations of these receptors are –
 D1 – Nigrostriatal pathway (putamen, nucleus accumbens and olfactory
tubercle). Its inhibition causes extrapyramidal disorders.
 D2 – Striatum, substantia nigra and pituitary. It is involved in the control of
the behavior, voluntary movements, prolactin release and other endocrine
consequences.
 D3 – Midbrain, nucleus accumbens and hypothalamus.
 D4 – Mesocortical pathway (frontal cortex, medulla and midbrain). Some
of the atypical neuroleptics possess D3 and D4 antagonistic activity, but
their exact role in schizophrenia is not yet fully established.
 D5 – Hypothalamus and hippocampus. Its exact role is not known.

15. Dopamine synthesis

16. Acetyl choline
 First neurotransmitter discovered & described as vagus stuff by Otto Loewi
 Known to be neurotransmitter at autonomic ganglia
 It is mainly found in interferon's
Synthesis
 Glucose enters the nerve terminals by passive transport
 Glycolysis occur in neuronal cytoplasm & pyruvic acid molecules are
generated
 Pyruvate mitochondria and an acetyl group is derived from pyruvic
acid + coenzyme-A present in mitochondria to form acetyl coenzyme-A
 Ach is actively transported to neuronal terminal from synaptic cleft (via
sodium & choline transporters)
 Ach is synthesized in cytoplasm of nerve terminal from choline & acetyl
coenzyme-A in presence of an enzyme choline acetyltransferase
 Ach is transported to vesicles and stored
 Released in to synaptic cleft by exocytosis

17. Acetyl choline synthesis

18. Regulations in neurotransmission release
 Located on specialized release sites on presynaptic memberaine
 Neurons communicate with each other through NTs highly localized Ca⁺⁺
influence act as stimulus to rapid release of NT
 Activation of presynaptic receptors closes a feedback loop which leads to
enhancement or inhibition of NTs release
 These receptors are called as auto receptors
 Presynaptic receptors are several types include both G protein linked
(metabotropic) & multi unit ion channel (ionotropic) types
 Activation of G-protein linked receptors leads to reduction in evoked NT
release closes negative feed back loop
 Activation of ionotropic releases NT as a result ability to raise the calcium
ions in the terminals directly
 Presynaptic terminals may also have receptors responding to NTs released
from neurons


19.  Activation of hetero receptors influence the release of NTs
 Presynaptic receptors are important from neurophysiological point of view
& as potential targets for therapeutic agents
 Neurotropic factors :-
 These neuropeptides produced by neurons, astrocytes , microglia &
inflammatory cells assist in repair in tissue damage

20. References
Medical Pharmacology
Seventh Edition
KD TRIPATHI MD
Ex-Director-Professor and Head of Pharmacology
Maulana Azad Medical College and associated
LN and GB Pant Hospitals

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