Transcript Slide 1

Dr S Theegala
Neurotransmitter pathways
Receptor mechanisms
Receptor location
Neurotransmitter transporters
Questions – MCQs and EMIs
•Discovery of effective psychotropic medication – 1950
• Chlorpromazine – as an antihistamine
•MAO inhibitors - Discovered in the efforts to find
antitubercular drug
•Psychotropic drugs exerts their effects by altering
specific chemical processes involved in neuronal
•Research efforts led to discovery of
Neurotransmitter substances
Neurochemical pathways
•Synaptic unit – ‘The functional building block of
nervous system’
•Term ‘synapse’ – Charles Sherrington in 1897
•Types of synapses
•Communication between two neurons involves a
combination of bioelectrical and chemical processes
•Release of a neurotransmitter
•Subsequent activation of a receptor
•Activation of postsynaptic receptor
•Excitation/ inhibition
•Direct effect – ion channel
•Indirect effect
•Fast transmission
opening of ion
•Slow transmission
G protein stimulation or inhibition of an enzyme - or
of second messenger
Experiment by Otto lewi in 1921 offered first evidence of
chemically mediated neurotransmission
Ach, DA, NA, 5-HT
Histamine, Glutamate, GABA
Enkephalin , endorphin, substance p , Vasopressin ,
CCK ,NT, TRH,NPY, CRF and Orexins
Neurotransmitter pathways
•Long Ascending and descending axonal pathways
derived from discrete neuronal cell groups located
within specific brain nuclei
DA, NA,5-HT and Ach
•Long and short axonal- derived from neuronal cell
bodies widely distributed through out the brain
Glutamate and GABA
•Short intraregional pathways within cerebral cortex ,
striatum ,etc
Somatostain neurons in the cerebral cortex
Receptor mechanisms
•Directly coupled to an ion channel – ligand- gated ion
channel/ionotropic receptors
Fast transmission
NMDA, GABA A, 5HT3 and nicotinic Ach receptors
•G- protein receptors
When transmitter or agonist binds – either activate
or inhibit second messenger systems
1. Adenylate cyclase/cyclic adenosine
monophosphate (CAMP)
2. Phospholipase C/Inositol triphosphate /
 DA, NA, 5-HT (except 5HT3), muscarinic Ach,
Adrenoceptors and GABA B
Receptor location
•Post synaptic
•Terminal auto receptor
•Somatodendritic auto receptor
•Presynaptic heteroceptors
Neurotransmitter transporters
• Most neurotransmitters are removed from synaptic cleft
by transporters
• Terminates neurotransmitters action on post and
presynaptic receptors
• Are single protein chains that cross neuronal membrane
• Are actually cotransporters transporting Na ions into the
• They are second major target for psychotropic drugs
•Neuronal cell bodies
Substantia nigra
Ventral tegmental area
•Synthesized from tyrosine
•Metabolized by MAO (B) and COMT
•Inhibitory auto receptor feedback regulation by
presynaptic D2 and D3 receptors
•5 receptors
D1 like – D1 and D5
D2 like – D2, D3 and D4
D1 , D2 – more wide distribution (striatal,
mesolimbic and hypothalamic)
D3 and D4 more localized
•Principal location of NA containing neurons
locus cerulus - axons projecting to limbic areas and spinal
Lateral tegmental area – projections to forebrain regions
•Cortical projections – arousal and alert state
•Limbic projections - drive , motivation , mood and response
to stress
•Synthesized from tyrosine
•Metabolized by MAO(A) and COMT
Alpha 1 and 2 – post synaptic sites
Alpha 2 also on noradrenergic terminals – acts as auto
Alpha 1 – excitatory; Alpha 2 – inhibitory
Beta 1,2 and 3 – stimulatory
Beta antagonists – reduction of performance anxiety
•Cell bodies – midbrain and brain stem raphe nuclei
Ascending pathways - fore brain regions (hippocampus,
striatum, amygdalae, hypothalamus and cerebral cortex)
o5- HT has a modulatory role in aspects of behaviour
including mood, emotion, sleep , wakefulness and
regulation of circadian functions , control of feeding
and sexual behaviours , body temperature , perception
and emesis.
Descending pathways
oDorsal horn of spinal cord (inhibition of pain
oVentral horn (regulate motor neuron input)
Serotonin (contd.)
•Synthesized from tryptophan
•Metabolized by MAO
•14 known 5 HT receptors
•All are G- protein coupled except 5 -HT3
5- HT 1A – important target in the action of
5- HT 2A – sensory perception
5- HT 2c- when activated reduce food intake, induce
5- HT3 – antagonists have antiemetic action
- regulates DA release in nucleus accumbens
5 –HT 6 - Modulate memory and attention
5-HT7 may be important in depression and circadian
•Acetylcholine - More diffuse distribution in the brain
•Cholinergic nuclei – basal forebrain and pons
•Nucleus basalis of meynert - cortex
•Lateral septum – hippocampus (memory dysfunction )
•Synthesized from – choline
•Nicotinic receptors - ion channel
Two basic types – muscle – found in neuromuscular
Neuronal – brain
•Muscarinic receptor - M1 – M5 all in brain
G protein coupled
•Widely distributed in the brain
•Highest densities – basal ganglia, hypothalamus, amygdalae
and other limbic areas
•Formed from glutamate
– ligand gated ion channel (Cl-)
Benzodiazepines, barbiturates, Zopiclone and alcohol
•GABA B- G protein linked
•Significance of them not well understood - important in
absence seizures, cognitive performance and regulation of
amine release.
•Excitatory amino acid
•Cell bodies - widely distributed in the brain
•Synthesized from glucose or from glutamine
•Role of glutamate transmission in psychosis (antagonists at
glutamate receptors)
•Glutamate Receptors
ligand- gated ion channels
oNMDA; AMPA; Kinate receptors
G- protein linked metabotropic channels
Which of the following statements regarding transporters is
A. Amphetamines do not gain entry to nerve terminals via
B. Inhibitors of GABA transport do not have
anticonvulsant activity
C. Neurotransmitter transporters are electrogenic
D. There are five types of GABA transporters
E. Transporters do not terminate neurotransmitter action
on post and pre-synaptic receptors.
Answer: C
Which of the following statements regarding orexins is
A. They do not have an effect on schizophrenia
B. They do not have an effect on response to stress
C. They do not have an effect on circadian rhythm
D. They are not important in regulation of feeding
E. The ox1 and ox2 are highly expressed on cortex
Answer: A
Which of the following statements is true?
A. Anandamide is endogenous against of CB1 and CB2
B. CB1 receptors are found in brain and are potential
targets for immune system
C. CB2 receptors are associated with treatment of pain
and various mood disorders
D. CCK receptor antagonists are successful anti panic
E. Neurotensin has been postulated as a possible target
for treating mood disorders.
Answer: A
Which of the following is ligand gated receptor?
A. 5-HT 1A
B. Muscarinic acetylcholine
C. D2
Answer: E
Which of the following is G protein coupled receptor?
A. 5-HT 3
B. Nicotinic acetylcholine
Answer: D
A neurotransmitter released from a neuron regulates its own
release by interacting with
A. Presynaptic hetero receptors
B. Post synaptic receptors
C. Terminal auto receptors
D. Somatodendritic auto receptors
E. Terminal hetero receptors
Answer: C
A neurotransmitter released from a neuron affects neuronal
firing by interacting with
A. Presynaptic hetero receptors
B. Post synaptic receptors
C. Terminal auto receptors
D. Somatodendritic auto receptors
E. Terminal hetero receptors
Answer: D
Theme: Neurotransmitters and its precursors
A. Acetyl Co A
B. Tyrosine
C. Tryptophan
D. Glutamine
E. Glutamate
F. Glycine
G. Glucose
H. Glucosamine
I. Homovanillic acid
Choose one suitable precursor for the following neurotransmitters
1. Serotonin
2. Noradrenalin
Theme: Serotonin receptors
a. 5 HT 1
b. 5 HT 2
c. 5 HT 3
d. 5 HT 4
e. 5 HT 5
f. 5 HT 6
g. 5 HT 7
Choose one suitable receptor for the following actions
1. Nausea and emesis
2. Circadian rhythm and thermoregulation
3. Adaptive response to stress
Thank you