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Summary of psychopharmacology UU
Psychopharmacology overzicht neurotransmitters en hun werking
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PSYCHOPHARMACOLOGY
LECTURE 1.
What is a drug or a pharmacon?
o An administered substance that influence physiological processes
o Sometimes a drug is also body’s own substances
o You don’t call it a pharmakon if it’s (primarily) a nutrient
Psychoactive substances influence processes in the brain, and as a result influence behavior,
cognition and emotions (affect). They can be used for different purposes:
o Therapeutic
o Recreational
→ Which two overarching classes of psychoactive substances can be discerned based on their use?
- Therapeutic and Recreational drugs
What is psychopharmacology?
o Pharmacology studies the influence of substances on biological processes of living beings
o Psychopharmacology focuses on the effect of substances on behavior, cognition and affect,
including their mechanisms in the brain
Pharmacokinetics: How does a substance move through the body?
→ Principles lecture
Pharmacodynamics: To what receptors does the substance bind?
What effect does the substance have on the receptor?
In psychopharmacology: Interactions with neurotransmitters
Neurotransmission:
o In the brain there are a lot of cells, the most important ones are neurons
o They communicate through action potentials
o A synaps at the end of an axon is activated and a chemical interaction takes place:
o A neurotransmitter is released in the synaptic cleft
o In order for this neurotransmitter to be released, it has to be
synthesized
o After it has been released, there is a form of degradation to
end the action on the post-synaptic neuron
o The pre-synaptic neuron fires the action potential, it arrives
at the post-synaptic neuron and through the receptors in the
membrane, this post-synaptic neuron is affected by the
neurotransmitters of the pre-synaptic neuron
Neurotransmitters work on neurons via receptors. This is
symbolized as a lock, where the neurotransmitter fits like a key.
(In real life the receptors are very complex)
,PSYCHOPHARMACOLOGY
The most typical receptors in the brain are the postsynaptic receptors. A lot of the effects of
neurotransmission depends primarily on the postsynaptic receptors. The post-synaptic neuron needs
some way of receiving the chemical message that is being transferred by the pre-synaptic neuron.
The three targets on the function of neurons that drugs influence are:
o Receptor activation
o Reuptake blockade
o Enzyme modulation
The function of neurons that is not a drug target is metabolite excretion.
The way metabolites are excreted from the body are typically not a physiological process that is
affected by drugs. Metabolites are the parts in which a molecule is dissembled before it is excreted
from the body. Typically these parts do not have a psychoactive effect anymore, so the way this is
excreted from the body is not a way for drugs to influence activity of neurons.
Neurotransmission: Activation of receptors.
o Intra- and extracellular space is divided by a membrane
o There is a potential difference inside and outside the nervecell (resting potential of ±-70 mV)
o Neurotransmitters act on neurons through receptors, and open the ion channel
• Effect: small change compared to the resting potential that can add up to the
threshold for an action potential. These changes make the chances of an action
potential being fired more or less likely
• This is EPSP, Excitatory Post Synaptic Potential: will reduce the potential
difference towards 0, which increases the chance of an action potential being
generated
• Or IPSP, Inhibitory Post Synaptic Potential: will increase the potential differences,
which reduces the chance of an action potential being fired.
There are a lot of chemical messengers in the synaps, and a lot of elements drugs can work on.
This is the chain in which a
neurotransmitter is released in the
synaptic cleft, for a dopamine
receptor.
There are about 100 billion
neurotransmitters in a human
body. Some of them are used in a
relatively low number of nerve
cells in the brain (<1%), such as
NE(norepinephrine),
DA(dopamine), and 5-HT
(serotonin).
They form relatively specific
targets for drugs.
Neurotransmitters that are frequently used in the body (~50%) are for example GABA (inhibitory)
and Glu(glutamate) (excitatory). Also the endocannabinoid receptor is present in many synapses.
,PSYCHOPHARMACOLOGY
These neurotransmitters have been implicated in quite some disorders, but it’s difficult to use a drug
that affects directly GABA or Glu because they are so abundant. When you use a drug that affects
GABA or Glu, you will affect almost the whole brain instead of affected only a subtype of these
neurotransmitters. When you use a drug that enhances or reduces the effect of a neurotransmitters
you have a lot of side effects because there are a lot of receptors in the brain that will also be
activated, even though they may not be part of the problem.
So where do the neurotransmitters come from?
They come from precursors, substances that are needed to create a neurotransmitter.
• Monoamines (single amine group)
o Catecholamines: DA, NE, E
▪ Precursor: Tyrosine. This comes from food. From tyrosine you can form:
• DOPA, DA(dopamine), NE(norepinephrine) and E(epinephrine)
o Indolamines: 5-HT
▪ Precursor: tryptophan
• Amino Acids:
o GABA, Glu
▪ Precursor: glucose
• ACh (Acetyl Choline):
o Precursor: choline, lecythine
• Peptides:
o Oxytocine, endorphines
▪ Precursor: amino acids
Different types of receptors:
- Post-synaptic, axo-dendritic (3)
Receptors that are located in a receiving neuron in the synaptic cleft. Receptors that
are activated by a combination of an axon and a dendrite. = the most typical type
- Presynaptic:
Autoreceptor(1), is quite close to the synaps. Can detect the releasing of a
neurotransmitter from its own axon terminal, and this typically has a feedback role.
When enough neurotransmitters are released, the transmission will be ended.
Heteroreceptor(4), is a receptor on a presynaptic neuron that reacts to the input
from another neuron. It modulates the synaps from another neuron.
Autoceptors on other locations in the cell, eg. on a dendrite (2).
Activation of these receptors can have very different implications for how it modifies the
neurotransmission. The most important communication between nerve cells comes from the
synaptic axo-dentritic receptor. But besides this there are other ways receptors can be activated:
- Retrograde transmission: cannabinoid system; post synaptic neuron releases
endocannabinoids that activate receptors on the presynaptic neuron, and can also end
neurotransmission.
- Non-synaptic diffusion: There is not really transmission between a pre-synaptic cell and a
post-synaptic cell that have a synaptic connection, but receptors on other parts of the
neuron can be activated. This is when the neurotransmitters floats away from the part where
it is released.
, PSYCHOPHARMACOLOGY
There are also neuromodulators. They don’t activate receptors directly but they modify receptors, so
that when a neurotransmitters binds to the receptor, the properties of the receptor are different.
An example is Endogenous Benzodiazepine.
And there are neurohormones: they are being released in the blood instead of in synaptic
communication, but can also activate receptors.
The most important neurotransmitters in the brain:
Only remember the subtypes when they are directly affected by a drug, but that is when they are
explicitly mentioned in the book. Otherwise you don’t have to know all different subtypes of all
different receptors.
After the neurotransmitter is released and the neurotransmission has started, it also has to be ended
at some point. The different neurotransmitters have different ways of how their transmission is
ended. Sometimes they are being degraded, sometimes reuptake takes place. There is thus a
combination of degradation (metabolism) in the synaps and reuptake within the cell.
For example:
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