Monoamine Neurotransmitters

Catecholamines and Serotonin are biogenic

amines that serve as transmitters of
neuronal or hormonal signals in a wide range
Monoamine Neurotransmitters
of physiologic processes.
Monoamines

Catecholamines
• Dopamine
• Norepinephrine
• Epinephrine

Indoleamines
• Serotonin
• Melatonin

Imidazolamine: Histamine
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.
 Locations of monoamine production and action
in the body
Monoamine type Site of production Mode of Site of action
transmission
Epinephrine Adrenal medulla Hormonal Cardiac muscles, smooth
(chromaffin cells) muscles and effects on
metabolism
Norepinephrine Sympathetic ganglia Neuroeffector cell Effector tissues include
junction cardiac muscles, smooth
muscles, vascular
endothelium and exocrine
glands
Adrenal medulla Hormonal Primarily cardiac and
(chromaffin cells) smooth muscles
Brain stem Neural synapse Widespread CNS neuronal
(locus coeruleus and connections
reticular formation)
Dopamine Midbrain (substantia Neuronal synapse Neuronal connections in
nigra) cerebral striatum
Midbrain Neuronal synapse Cerebral mesolimbic and
(ventral tegmentum) mesocortical neuronal
connections
Diencephalon Neuronal synapse Pituitary gland
(hypothalamus)
Retina Neuronal synapse Neuronal connection within
retina
Olfactory bulb Neuronal synapse Neuronal connection within
olfactory bulb
Gastrointestinal tract Autocrine/ Regulation of bicarbonate
paracrine secretion, gut motility, sodium
in exocrine secretions
Kidney (derived from Autocrine/ Regulation of natriuresis
circulating L dopa) paracrine

Serotonin Brain stem Neuronal synapse Widespread CNS neuronal

(raphe nucleus) connection
GI (enterochromaffin Paracrine/ platelet GI smooth muscles and
cells) uptake platelets
Biosynthesis
 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.
 Dopaminergic Neuron

After synthesis in the cytoplasm of presynaptic terminals,

it is loaded into synaptic vesicles via a vesicular monoamine
transporter (VMAT)
 Receptors
• D₁ like (D₁ and D₅)
• D₂ like (D₂, D₃, D₄)

• All dopamine receptors are metabotropic GPCR.

D1 and D2 receptors
 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.
 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
Degradation of catecholamines
Biosynthesis
 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

• 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.
• 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.

Degradation of catecholamines
Epinephrine
 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.
• 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.
• 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.
Direct effects of adrenergic activation on some
organ systems based on receptor subtype:
Mechanism of action
 Serotonin

• Neurotransmitter synthesized from tryptophan.

• Synonyms: enter-amine, thrombocytin.
• Chemically: 5-OH tryptamine(5- HT).
• Vasoconstrictor.

Sites:
Chiefly Gastrointestinal cells, CNS, Platelets.
Biosynthesis
• 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)
 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.
 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.
Receptors for Various Neurotransmitters
 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.
 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.
 Mechanism
Destruction of Dopaminergic neurons in
Substantia nigra

Caudate nucleus and putamen to

become overly active

Overexcite many or
Continuous output of all of the muscles of
body , thus leading to
excitatory signals. rigidity.
 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.