Neurotransmitte

1. Monoamine Neurotransmitters

2. Monoamine Neurotransmitters
Catecholamines and Serotonin are biogenic
amines that serve as transmitters of
neuronal or hormonal signals in a wide range
of physiologic processes.

3. Monoamines
Catecholamines
• Dopamine
• Norepinephrine
• Epinephrine
Indoleamines
• Serotonin
• Melatonin
Imidazolamine: Histamine

4. Chemical structure
• Catecholamines are phenylethylamines formed
from tyrosine.
• Dihydroxybenzene or catechol structure is sensitive
to oxidative formation of quinones in the presence of
air and light.

7. Locations of monoamine production and action
in the body
Monoamine type Site of production Mode of
transmission
Site of action
Epinephrine Adrenal medulla
(chromaffin cells)
Hormonal Cardiac muscles, smooth
muscles and effects on
metabolism
Norepinephrine Sympathetic ganglia Neuroeffector cell
junction
Effector tissues include
cardiac muscles, smooth
muscles, vascular
endothelium and exocrine
glands
Adrenal medulla
(chromaffin cells)
Hormonal Primarily cardiac and
smooth muscles
Brain stem
(locus coeruleus and
reticular formation)
Neural synapse Widespread CNS neuronal
connections

8. Dopamine Midbrain (substantia
nigra)
Neuronal synapse Neuronal connections in
cerebral striatum
Midbrain
(ventral tegmentum)
Neuronal synapse Cerebral mesolimbic and
mesocortical neuronal
connections
Diencephalon
(hypothalamus)
Neuronal synapse Pituitary gland
Retina Neuronal synapse Neuronal connection within
retina
Olfactory bulb Neuronal synapse Neuronal connection within
olfactory bulb
Gastrointestinal tract Autocrine/
paracrine
Regulation of bicarbonate
secretion, gut motility, sodium
in exocrine secretions
Kidney (derived from
circulating L dopa)
Autocrine/
paracrine
Regulation of natriuresis
Serotonin Brain stem
(raphe nucleus)
Neuronal synapse Widespread CNS neuronal
connection
GI (enterochromaffin
cells)
Paracrine/ platelet
uptake
GI smooth muscles and
platelets

9. Biosynthesis

10. Dopamine
• Major dopamine-containing area of the brain is the
corpus striatum, which receives major input from the
substantia nigra
• It plays an essential role in the coordination of body
movements.
• It is also believed to be involved in motivation,
reward, and reinforcement.

11. Dopaminergic Neuron
After synthesis in the cytoplasm of presynaptic terminals,
it is loaded into synaptic vesicles via a vesicular monoamine
transporter (VMAT)

12. Receptors
• D₁ like (D₁ and D₅)
• D₂ like (D₂, D₃, D₄)
• All dopamine receptors are metabotropic GPCR.

13. D1 and D2 receptors

14. Uptake
• Uptake is facilitated by transporters located in
neuronal and extraneuronal tissues:
1. Dopamine transporter (DAT)
2. Organic cation transporter
Cocaine apparently produces
its psychotropic effects by binding to and inhibiting DAT, yielding a
net increase in dopamine release from specific brain areas.

15. Catabolism
• It occurs by multiplicity of pathways, catalyzed by an
array of enzymes, resulting in wide variety of
metabolites.
1. Monoamine oxidase pathway (MAO)
2. Catechol O methyl transferase pathway (COMT)
Inhibitors of these enzymes, such as phenelzine is used
clinically as antidepressants

16. Degradation of catecholamines

17. Biosynthesis

18. Norepinephrine
• Neurotransmitter in the locus coeruleus, a brainstem
nucleus that projects diffusely to a variety of
forebrain targets
• It influences sleep and wakefulness, attention, and
feeding behavior.
• Synthesis requires dopamine β-hydroxylase

19. • Norepinephrine is then loaded into synaptic vesicles
via the same VMAT involved in dopamine transport.
• Norepinepherine is cleared from the synaptic cleft by
the norepinepherine transporter (NET).
• Like dopamine, norepinepherine is degraded by MAO
and COMT.

20. • Within 2-5 minutes, these molecules are catabolized
in tissues, by catechol-O-methyltransferase (COMT),
and then by monoamine oxidase.
• The major end product is 3-hydroxy-4-methoxy
mandelic acid or vanillylmandelic acid(VMA).
• Normal excretion of VMA is 2-6 mg/day.

21. Degradation of catecholamines

22. Epinephrine

23. Epinephrine
• Is found in the brain at lower levels
• Epinephrine is loaded into vesicles via the VMAT.
• Epinephrine acts on both α- and β-adrenergic
receptors.

24. • Catecholamines acts through metabotropic type of
receptor
• Activation of α₁ adrenoreceptors is excitatory.
• Activation of α₂ adrenoreceptors is inhibitory.
• Activation of α1 receptors usually results in a slow
depolarization linked to the inhibition of K+ channels,
• while activation of α2 receptors produces a slow
hyperpolarization due to the activation of a different
type of K+ channel.

25. • Nor epinephrine secreting neurons are called
noradrenergic and epinephrine secreting are called
adrenergic neurons.
• The chemical transmitter present at most
sympathetic postganglionic endings is nor
epinephrine.
• Both epinephrine and norepinephrine act on α and β
adrenergic receptors.
• Nor epinephrine have a greater affinity for α and
epinephrine have a high affinity for β receptors.

26. Direct effects of adrenergic activation on some
organ systems based on receptor subtype:

27. Mechanism of action

28. Serotonin
• Neurotransmitter synthesized from tryptophan.
• Synonyms: enter-amine, thrombocytin.
• Chemically: 5-OH tryptamine(5- HT).
• Vasoconstrictor.
Sites:
Chiefly Gastrointestinal cells, CNS, Platelets.

29. Biosynthesis

30. • Loading of 5-HT into synaptic vesicles is done by the
VMAT
• Effects of serotonin are terminated by transport back
into nerve terminals via a specific serotonin
transporter (SERT).
• Many antidepressant drugs are selective serotonin
reuptake inhibitors (SSRIs)

31. CNS functions regulated by 5HT (serotonin)
• Serotonin is a stimulator of brain activity, hence its
deficiency causes depression.
• Serotonin is a powerful vasoconstictor and results in
smooth muscle contraction in bronchiloes and arteries.
• Sensitivity to pain is reduced by serotonin.
• Serotonin controls the behavioural patterns, sleep, blood
pressure and body temperature
• Serotonin evokes the release of peptide hormones from
gastrointestinal tract.

32. Receptors
• Only one group of serotonin receptors, called the 5-
HT3 receptors, are ligand-gated ion channels
• These are non-selective cation channels and
therefore mediate excitatory postsynaptic responses.

33. Receptors for Various
Neurotransmitters

34. Parkinson’s disease
• Also known as paralysis agitans.
• Results from widespread destruction of that portion
of substantia nigra(pars compacta) that sends
dopamine secreting nerve fibres to caudate nucleus
and putamen.

35. Characterized by:
• Rigidity of musculature of body
• Involuntary tremors (intention tremors)
• Serious difficulty in initiating movement (akinesia).
• Imbalance of posture, dysphagia, impaired ability to
swallow, speech disorders, gait disturbances and
fatigue.

36. Mechanism
Destruction of Dopaminergic neurons in
Substantia nigra
Caudate nucleus and putamen to
become overly active
Continuous output of
excitatory signals.
Overexcite many or
all of the muscles of
body , thus leading to
rigidity.

37. Treatment:
• L-DOPA: Converted to dopamine in brain.
• L- Deprenyl: Inhibits MAO responsible for
destruction of most of dopamine after it has been
secreted.
• Therefore, any dopamine that is released remains in
the basal ganglia for long time.
• L-DOPA + L-Deprenyl is useful.