Neurotransmitters transmit signals between neurons through synapses. The four main criteria for identifying neurotransmitters are that they must be synthesized in neurons, released during neuronal activation, produce a response in target cells, and be removed from synapses. Major neurotransmitters include amino acids (glutamate, GABA), monoamines (dopamine, norepinephrine, serotonin), peptides, and acetylcholine. Neurotransmitters are packaged into vesicles and released into the synaptic cleft through exocytosis. They then bind to receptors on the target cell and are inactivated through reuptake or enzymatic breakdown.

2. Neurotransmitters are endogenous chemicals that
transmit signals across a synapse from one neuron (nerve
cell)to another 'target' neuron.
Synapses are the junctions where neurons release a
chemical neurotransmitter that acts on a postsynaptic
target cell, which can be another neuron or a muscle or
gland cell
Neuromodulators are chemicals released by neurons
have little or no direct effects on their own but can modify
the effects of neurotransmitters.

3. Until the early 20th century, scientists
assumed that the majority of synaptic
communication in the brain was electrical.
The histological examinations by Ramón y
Cajal (1852–1934), a 20 to 40nm gap
between neurons, known today as the
synaptic cleft, was discovered. The
presence of such a gap suggested
communication via chemical messengers
traversing the synaptic cleft.
In 1921 German pharmacologist Otto
Loewi (1873–1961) confirmed that neurons
can communicate by releasing chemicals.
Through a series of experiments involving
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4. There are four main criteria for identifying
neurotransmitters:
1. The chemical must be synthesized in the neuron or
otherwise be present in it.
2. When the neuron is active, the chemical must be released
and produce a response in some target.
3. The same response must be obtained when the chemical is
experimentally placed on the target.
4. A mechanism must exist for removing the chemical from
its site of activation after its work is done.
IDENTIFICATION

5.  Amino acids: glutamate, aspartate, D-serine,
γ-aminobutyric acid, glycine.
Monoamines: dopamine, Norepinephrine,
Epinephrine, histamine, serotonin.
Trace amines:
phenethylamine, tyramine, 3-iodothyronamine,
octopamine, tryptamine.
Peptides: somatostatin, substance P, cocaine
and amphetamine regulated transcript, opioid
peptides.
Gasotransmitters: nitric oxide (NO), carbon
monoxide (CO), hydrogen sulfide (H2S)
Others: acetylcholine (ACh), adenosine,
Anandamide.

6. Reuptake
• From the synaptic cleft back into the cytoplasm of the
neuron
The reuptake systems employ two families of
transporter proteins:
 They include transporters for Norepinephrine,
dopamine, serotonin, GABA, and glycine, as well as
transporters for proline, taurine, and the acetylcholine
precursor choline. In addition, there may be an
epinephrine transporter.
 The other family is made up of at least three
transporters that mediate glutamate uptake by
neurons and two that transport glutamate into
astrocytes.

7. VMAT1 & VMAT2:
Both have a broad specificity, moving
dopamine, Norepinephrine,
epinephrine, serotonin, and
histamine from the cytoplasm into
secretory granules.
• There is also a vesicular GABA
transporter (VGAT) that moves GABA
and glycine into vesicles and a
vesicular acetylcholine transporter.

8. 2-acetoxy-N,N,Ntrimethylethanaminium
Struct
ure:
Acetylcholine was the first neurotransmitter to be discovered.
Isolated in 1921 by a German biologist named Otto Laewi.
Precursor: choline
Acts on: nicotinic receptors and muscarnic receptors
Inactivated by acetyl choline esterase enzyme or reuptake by
vesicular acetyl choline transferase (VAchT)

10. Vasodilation,
cardiac inhibition,
GI peristalsis;
control of thought,
mood, sleep, muscles,
bladder, sweat glands

11. There are three
Catecholamines :
1.Dopamine
2.Epinephrine
3.Norepinephrine

14. Precursor : Tyrosine (amino acid)
Synthesis site : Adrenal medulla
Acts on alpha (α) and beta (β)
adrenergic receptors
Inactivation is done by MAO and by
catechol-O-methyl transferase (COMT)

15. α & β Receptors
• Epinephrine and Norepinephrine both act
on α and β receptors, with
norepinephrine having a greater affinity
for α-adrenergic receptors and
epinephrine for β-adrenergic receptors.

17. Synthesized from the amino acid tyrosine.
Generally involved in regulatory motor activity, in
mood, motivation and attention.
Functions :
1. Induction of vomiting
2. Inhibition of prolactin secretion
3. Stimulation of GnRH
4. Schizophrenia
5. Control of movements(parkinsonism)
Schizophrenics have too much dopamine.
Patients with Parkinson's Disease have too little

18. Five different dopamine receptors (D1, D2,
D3, D4, D5) are known and exist in multiple
forms.
Most, but perhaps not all, of the responses
to these receptors are mediated by
heterotrimeric G proteins.
Overstimulation of D2 receptors is thought to
be related to schizophrenia.
D3 receptors are highly localized, especially
to the nucleus accumbens
Dopamine Receptors

19. Serotonin
Also known as 5-hydroxy tryptamine
Precursor : Tryptophan
It is found within the brain stem in the
midline Raphé nuclei,
It is present in highest concentration in
blood platelets and in the gastrointestinal
tract
It is inactivated by the action of the MAO
which converts it into
5-hydroxyindoleacetic acid

21. Serotonergic Receptors
• 5-HT1 - 5-HT7 receptors
• Most of these are G protein-coupled receptors
• 5-HT1 => 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, & 5-HT1F
• 5-HT2 => 5-HT2A, 5-HT2B, & 5-HT2C
• 5-HT2A -platelet aggregation and smooth muscle
contraction.
• 5-HT3 -ligand-gated ion channels present in the GIT
are related to vomiting.
• 5-HT4 -in the GIT, where they facilitate secretion
and peristalsis.
• 5-HT5 => 5-HT5A & 5-HT5B
• 5-HT6 & 5-HT7-distributed throughout the limbic
system

22. (γ-amino butyric acid)
Major inhibitory mediator in the brain, including being
responsible for presynaptic inhibition.
Precursor : glutamate
Reuptake by vesicular GABA transferase
Metabolized primarily by transamination to succinic
semialdehyde
GABA transaminase (GABA-T) catalyzes the
transamination.

23. Three subtypes of GABA receptors have been
identified: GABAA, GABAB, and GABAC
The GABAA and GABAC receptors are ion
channels made up of five subunits surrounding a
pore . In this case, the ion is Cl– .
The GABAB receptors are metabotropic
,coupled to heterotrimeric G proteins that
increase conductance in K+ channels, inhibit
adenylyl cyclase, and inhibit Ca2+ influx.
GABA Receptors

25. Peptides that bind to opioid receptors are
called opioid peptides.
The ENKEPHALINS are found in nerve endings
in the gastrointestinal tract and many different
parts of the brain, and they appear to function
as synaptic transmitters.
They have analgesic activity when injected
into the brain stem.
They also decrease intestinal motility.

26. RECEPTORS
µ , κ , δ
All three are G protein-coupled
receptors, and all inhibit adenylyl cyclase.
Activation of µ receptors increases K+
conductance, hyperpolarizing central
neurons and primary afferents.
Activation of κ and δ receptors closes
Ca2+ channels.

28. General mechanism of action

38. Acetylcholine esterase