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Psychopharmacology overzicht neurotransmitters en hun werking
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Psychopharmacology
Psychologie Jaar 2 UU
Lectures
►Lecture 01: Introduction
Joke Baas
A Drug/Pharmacon is an administered substance that influences physiological processes.
Sometimes it is possible that this substance can already be found in one’s own body, like
insulin. Psychoactive Substances somehow influence processes in the brain and with that,
behaviour, cognition, and affect. They can be used for therapeutic (to cure a disease) and
recreational purposes. Pharmacology studies the influence of substances on biological
processes of living beings. So, psychopharmacology focusses on their effect on behaviour,
cognition, and affect, including their mechanisms in the brain. Not only are some medicines
classified as psychoactive drug but also think about more general product like coffee or beer
that function the same way a medicine does. With most drug use there are risks or unintended
Side Effects. It is important to evaluate the weight of those side effects for each patient so
that the side effects do not outweigh the beneficial effects of using the drug.
In pharmacology we ask ourselves two questions relating to the two main topics.
→ In Pharmacokinetics we ask ourselves ‘How does a substance move through the
body?’. So, the question here is not particularly what the drug does, but how it is transported.
→ In Pharmacodynamics we are more interested in questions like ‘To what receptors
does the substance bind?’ and ‘What effect does the substance have on the receptor?’. The
dynamics are more focussed on the interactions with neurotransmitters, and what the drug
does.
■ Neurotransmission (Brush-up)
In short, the neurons communicate with one another through action potentials. When this
arrives at the synapse, a chemical process called Neurotransmission starts. In this process
certain Neurotransmitters are emitted in the synaptic cleft. Before these transmitters can be
emitted, they must be present or Synthesized in the presynaptic neuron. After the release
there also has be some Degradation so that the presynaptic neuron stops the release of the
neurotransmitter. The released neurotransmitters then can bind to complex protein chains
called Receptors. The receptors located postsynaptic are most abundantly present. Not only
receptor activation on the postsynaptic neuron influences the functioning of neurons, but also
reuptake blocking, and enzyme modulation have this effect. Metabolite excretion does not
influence the functioning of neurons. Neurotransmission refers to the activation of receptors
through neurotransmission. To get a concrete idea on this process we will look at the
Dopamine example. To begin, there needs to be Tyrosine, an amino acid and natural building
block of the body, that can be obtained from one’s diet. Tyrosine will be transformed into
DOPA that in turn becomes Dopamine inside of the presynaptic neuron. After the
synthesizing of dopamine, the particles are bundled in Vesicles which allow the
neurotransmitters to be emitted in the synaptic cleft to be absorbed by the dopamine receptors.
,Not all neurotransmitters are equally used in the brain. For example, transmitters like
norepinephrine and serotonin are only used by less than 1% of your neurons, this also means
that finding drugs that interact with these transmitters results in relatively specific targets.
GABA and Glutamate on the other hand are roughly used by 50% of your neurons.
With these more frequently used transmitters the problem of specificity arises. When a
neurotransmitter is used so much in general functioning by the brain and can be traced back to
multiple regions and cortexes, implementing a drug that interferes with this transmitter can
have more effects throughout the brain than the one that was intended. In short, this means
that there will be a lot of side effects with the use of that drug.
In terms of neurotransmission forms we can distinguish several types. Firstly, we have the
most typical form of neurotransmission, the Synaptic Axo-Dendritic Transmission. Here,
the transmitters are transported through the synaptic cleft to the receptors on the postsynaptic
neuron. Besides this we also have the Retrograde Transmission where the postsynaptic
neuron releases Endocannabinoids that activate receptors on the presynaptic neuron that can
end the neurotransmission. Next, we have the Nonsynaptic Diffusion. There is no
transmission between two neurons through synapses. Receptors on other parts of the neuron
can be activated due to neurotransmitters diffusion where transmitters float through the
interneural space.
Neuromodulators do not activate receptors directly; however, they modify receptors. When a
neuromodulator binds to a receptor it changes its properties.
Neurohormones are not released in the synaptic cleft or any neural space. Neurohormones
are released in the blood and can therefore activate receptors that are further away.
The picture below provides information on general functions and neurotransmitters:
You only need to know the subtypes that are mentioned in the book
In summary, specific neurotransmitters have their own respective function, path, and
receptions. They also have their own method of ending neurotransmission activity.
It can be accomplished through a combination of degradation (metabolism) in the synapse and
reuptake within the cell. Ach for example is broken down outside of the cell and then the
particles are reabsorbed into the cell for later use. This means that Acetylcholine is processed
with Extracellular Degradation and Reuptake.
,▲ Precursors
For the actual construction of neurotransmission Precursors are needed. Precursors are
substances that are needed to build the neurotransmitters. For the Monoamines (Dopamine,
Norepiphrine, Epiphrine) the precursor is tyrosine.
→ For the Indolamines (Serotonin) the precursor is Tryptophan. The following
image shows the journey from tyrosine to Adrenalin (Epiphrine).
→ For Amino Acids like Glutamate and GABA the precursor is Glucose.
→ For Acetylcholine the precursor is Choline/Lecithin.
→ For the Peptides (Oxytocin & Endorphins) the precursors are amino acids.
▲ Receptors
There are also various types of receptors to which neurotransmitters can bind to. The most
typical type is the Axo-Dendritic Receptor where a receptor is located postsynaptic. There
are also several presynaptic receptors. The Autoreceptor sits relatively close to the synapse
and can detect the neurotransmission form its own axonterminal. Because of that is has a
feedback-oriented role which means it registers the released neurotransmitters and signals the
axon to stop emitting when activated. Autoreceptors are not solely found close to the synapse
but also around the soma and dendrite for example. Subsequently there is the Heteroreceptor
which modulates the synapse from another neuron.
1: Autoreceptor located on the synapse.
2: Autoreceptor located on the soma.
3: Postsynaptic receptor.
4: Heteroreceptor.
▲ Neurology and Drugs
With what we now know about neuroanatomy and the rules of
neurotransmission we can examine ways that drugs function in the
brain. The first of these points of engagement for drugs is the amount
of available transmitter. This can be altered and regulated through
various ways.
→ The presence of the precursor can be altered (1).
→ The activity of enzymes can be modulated (2).
→ The amounts of uptake can be regulated (3).
→ The transmitter release from the vesicles can be altered (4).
→ You can block the receptor (5).
→ Lastly you can block the reuptake (6) or degradation (7).
, ■ Pharmacology Background
Most insights from the study of pharmacology were found by accident and passed down form
generations. The effects of alcohol and other natural substances were widely known but
examined much later in time. Today, we try to look more at studies with hypotheses and
research programs in pharmaceutical industry and universities that are targeted at drug
discovery. To registrate a new drug a lot of data must be provided. Registration must be based
on research into the efficacy and the safety of the drug before it can be registered. In
preclinical phases, where animal research precedes administration to humans, there has to be
evidence for the efficacy, safety and the question of administration has to be answered (Does
the substance survive the gastro-intestinal system, or does it cross the blood-brain barrier?).
In the following clinical trials with humans there are 4 phases:
→ Phase 1: Experimentation to answer the question if the substance is toxic or
tolerable. So, here in the first phase they test whether human subjects tolerate the substance
(there is a Cost/Benefit consideration)
. → Phase 2: Limited efficacy studies. If the substance is proven to be sufficiently safe,
the next phase starts where they test if the substance really works against the disease. Most
often this phase starts with a smaller number of people who take the new drug.
→ Phase 3: Large, multi-centre studies. The question is ‘Does it work and is it better
than other existing drugs?’. When the results from phase 2 are good, larger trials start with
larger groups. In this phase, the new drug is first tested against a placebo and then against
existing drugs.
→ Phase 4: After the drug was registered phase 4 begins where the optimal dosing a
lesser side effects are noted. This is the phase of quality control and examining long term
effects of the drug. Phase 4 is important because major side effects usually do not come to
light until this phase.
In terms of drug safety one test is done. The Therapeutic Index examines the relation
between the Lethal Dose and the Effective Dose.
Therapeutic Index = LD50 * ED50
50 is the percentage of people showing the effect. The higher the index the better. So, for the
registration the therapeutic index needs to be high enough, other drug interactions need to be
known, and lastly the toxicity or side effects must be charted (the expected, unexpected and
the toxic dose, TD50).
The golden standard in drug research has a randomised design with a placebo-controlled
group. Also, it must be double blind to eliminate possible bias.
►Lecture 02: Principles
Kenemans
This lecture is devoted to the known issues and subjects that we encounter in later chapters
but are big enough to stand on their own in this lecture. We refer to psychoactive substances
as substances that influence behaviour if taken effectively. Remember that psychology is the
study of understanding, predicting and ultimately changing behaviour. Everyone uses these
substances, and their efficacy is determined by the intake method, the dosage, the situation,
and other factors. Psychopharmacology is important because:
→ It is about common use of substances that affect our behaviour.
→ The substances have a lesser commonly used improving effect on behaviour in that
some substances can reduce negative behaviour or increase positive.
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