Monoamines = catecholamine and trace amine

Catecholamine
In general monoamines dont seem to transmit specific information.
Many of the them are metabotropic and many of them are widespread.
Catecholamines are epinephrine, norepinephrine, dopamine.
Dopamine is abbreviated as DA. It is synthesized from several steps
from an essential amino acid called tyrosine. Tyrosine L-Dopa which
is the precursor of dopamine. There are few ? in the locus coeruleus of
the pons which is the main site of production of norepinephrine.
Norepinephrine is only a small change to dopamine and the only
neurons that have enzymes that catalyze this reaction are in the locus
coeruleus of the pons. All other neurons stop at this level. We have
adrenalinergic neurons and dopaminergic neurons. The only time the
neurotransmitter is synthesized not in the soma but during axoplasmic
transport. Even the neurons in the locus coeruleus package into the
synaptic vesicles dopamine. The last step in synthesis is done while
they are transferred to the terminal buttons. So they release
norepinephrine which makes them adrenalinergic receptors.
Monoamines termination response can be done by reuptake, but also
they have enzymatic destruction is being done by monoamines
oxidase MAO.
There is a drug called monoamine oxidase inhibitor. We use it for
depression. It inhibits the enzymatic activity of monoamines oxidase.
Monoamines are not degrades so it act as an agonist. So it is an
antidepressant as it increase the effect of dopamine norepinephrine
and serotonin. Monoamines oxidase have many receptors
; monoamine oxidase A and B . when we use a monoamine oxidase
inhibitor we should be careful because monoamines are also in the
blood, and in the blood monoamines have a function to regulate blood
pressure. They increase blood pressure. So if we take monoamines
oxidase we should be on a diet to prevent the uptake of monoamines
in wine meet.
Dopamine
Unlike other neurotransmitter systems dopamine has a very precise
distribution system. It exists in certain pathways and each one of them
has a particular function. There are 3 very important dopaminergic
pathways :
1-nigrostriatal pathway : goes from the substantial nigra to the corpus
striatum. The substantial nigra is part of the tectum in the midbrain.
The corpus striatum is the basal ganglia. Another way to say the basal
ganglia which is in the telencephalon.
2-mesolimbic system = from the midbrain to the limbic system. From
the VTA in the midbrain called the ventral tegmentum area. It goes to
several areas in the limbic system mostly the amygdala, the nucleus

accumbens. The nucleus accumbens is usually called the pleasure

center. It mediates the reinforcement activity of learning. Highly
implicated in addiction.
3- the mesocortical system which is a large system . it also goes from
the VTA. The VTA has several clusters of dopaminergic neurons that
send the projections off one to the nucleus accumbens and the other
one to all areas of the cortex : frontal cortex, parietal cortex,
temporal
the one in the cortex is involved in attention and its malfunctioning is
implicated in ADHD. ADHD is decreased dopaminergic activity in the
frontal cortex which leads to less ability to focus attention. Both the
mesolimbic and the mesocortical routes are associated with the
positive symptoms of schizophrenia. The nigrostriatal pathway is
implicated in Parkinson disease. We have movement troubles because
dopamine is also involved in movement. So in terms of functions we
have movement, schizophrenia, attention and learning and memory
and addiction. For the Study of drug abuse, the dopaminergic system is
very important.
The receptors : we have 6 receptors D1, D2, D3, D4, D5, D6. But
recently they have been rearranged according to their structure and
affinity to certain drugs.
We have now the D1-like family which includes D1 and D5.
The D2 like family includes D2 and D3. The existence of D6 is under
debate.
D1 and D5 are cAMP second messenger metabotropic receptors.
They mainly exist in the mesolimbic and mesocortical sytems.
The D2 like family is also metabotropic and exists mostly in the
nigrostriatum.
This not an absolute distribution but just in terms of concentration.
Each one has its own gene, so their separation has ground.
Drugs :
1-Cocaine : it is a dopaminergic reuptake blocker. It blocks the
reuptake of dopamine. It is therefore a dopaminergic agonist. Cocaine
comes from the coca leaves which is native from Bolivia and peru
where it is legal. The leaf itself has 13 drug in it. The leaf themselves
are not that addictive because the other 12 drugs mediate the effect of
cocaine. It was in coca cola until 1926. It is basically a stimulant but it
also produces euphoria. Cocaine is refined mostly now in mexico.
2-L-Dopa: works on Parkinson
3- reserpine: comes from bark in india which makes you ???, it is a
dopaminergic antagonist. It is antihypertensive. it makes the vesicles
of dopamine leak. So when we have an action potential at the terminal
buttons , the vesicles are empty because dopamine has leaked before.
Nothing comes to the synapse. This is a dopaminergic antagonist.
4- drug used for ADHD is Ritalin : it is a dopaminergic reuptake blocker.
It does the exact same thing synaptically as cocaine but one drug we

give at 9 euros the other we get 20 years to life. But pharmacologically

speaking they do exactly the same thing. Why Ritalin works on ADHD
patients ? this tell us that it is not easy to jump from a mechanism of
function to a behavior. The system is so complex.
5- chlorpromazine and haloperidol they were used as the primarily
antipsychotic drugs that we have. So schizophrenia. They are D2
receptors blockers, they are dopamine antagonist. They decrease
dopamine which elevate the positive symptoms of schizophrenia. But
we dont use them any more. We use Clozapine which works on other
receptor and which we call 3rd generation antipsychotics.
Norepinephrine
Or noreadrenaline = above the kidney. For the neurotransmitter we
say epinephrine or norepinephrine. For the receptor and the system we
use adrenal system or adrenergic receptors. Synthesis comes from
neurons in the locus coeruleus. It is destroyed by monoamine oxidase
A.
Distribution.it is mostly a neuromodulator not a neurotransmitter. It is
released rarely at the buttons. It is usually released at the axonal
varicosities. They are swelling at the axon which are release zones
where norepinephrine is released out the vesicles and where norepi
goes to the extracellular fluid and acts on many receptors in the
neighborhood. It is widely distributed in the central nervous system.
No precise pathways. And in the target organ of the sympathetic
nervous system. In the central nervous system norepi is in the synapse
inhibitory. But activation of the system is behaviorally excitatory. The
receptors are called alpha and beta. We have an alpha 1 and alpha and
beta 1 and beta 2. All of them are metabotropic which work on cAMP.
The function of the system is wakefulness and alertness.
Drugs : we use a beta blocker for hypertension. Antagonist
In general all drugs that work on dopamine also work on adrenergic
receptors but the affinity is less. And vice versa.
1- adrenergic agonist : amphetamine. It does not exist in nature. It is
made. They are chemically so similar to norepinephrine so in the
synapse they act like norepinephrine. They are receptors agonists.
Serotonin
It is derived from another essential amino acid called tryptophan. This
is why it is classified as an andolamine. It can be destroyed and have a
reuptake mechanism just like dopamine. Serotonergic neurons are
found in the Raphae nucleus which is in the core of the brainstem.
There is at least 9 clusters of neurons in the raphae that produce
serotonin. And from there they go everywhere, down the cord and into
the cortex. They dont have like dopamine a precise projection system,
they are more like norepinephrine , widespread. They are involved in
the regulation of movement but also regulate sensation and perception

of particular pain and vision. They also regulate aggression and feeding
what we call species-specific behaviors. Most of the time they are
inhibitory synaptically speaking.
The receptor system of serotonin is complex, there is 2 different
systems , one is called the M system , the other is called the D system.
The M system is called like this because it comes from the medial
raphae nucleus. It froms axonal varicosities therefore has no synapses
and this is why it is considered as neuron modulator. The D system
does form synapses and at those sites serotonin is a neurotransmitter.
There are at least 7 serotonin receptor type. Each one has a subtype
they are abbreviated as 5HD1, 5HD2 the 5HD1A has an authority
recently because in the frontal cortex it might regulate the effect of a
particular interest in drugs.
All of them are metabotropic.
Functions : arousal and sleep also.
Drugs :
1- Prozac is called an SSRI. Antidepressant medication like
monoamine oxidase inhibitors increase all monoamines. This is a
lot of side effects because yes we increase serotonin but we also
increase dopamine and norepinephrine. So this is why prosac is
only a SSRI a specific serotonin reuptake inhibitor.
2- LSD , synthesized by Hoffman accidently in Hoffman in 1938. Not
abused anymore like in the 1960s. its toxicity is very low. The
main problem of LSDs are bad trips. Bad nightmares and
flashbacks which are equivalent to episodes of post traumatic
disorders.
Amino acids :
Histamine : is comes from an amino acid. It has a wide distribution.
Several subtypes receptors and works primarily on mediation of pain.
neurotransmitter of the brain are glutamic acid and GABA.
Bose of them have a wide distribution. Most cortical excitation are of
glutamic acid origin . most cortical inhibitions are gabanergic. They
much more dominant than acetylcholine or dopamine. They have
multiple pathways, several precursors and most of them ionotropic.
Glutamate . MDMA receptor. It is found in very simple organs and
perhaps the very first neurotransmitter signaling substance to have
evolved on planet earth. It has several effects including not just
increasing the firing rate of neurons but also lowering their threshold of
excitation. High distribution. MSGs in Chinese food, Monosodium
glutamate. It does not cross the blood brain barrier. so it must act on
peripheral sites.
Drugs : AngelDust. It is a glutaminergic agonist. Very unpleasant
effects. It can to the Parkinson-like symptoms.