TUTORIALS – PSYCHOPHARMACOLOGY
How do drugs work? What class of drug is it?
What are their advantages and disadvantages?
What is their efficacy?
- How do we think about the disorder (the drug is targeting)?
https://referencelist.library.maastrichtuniversity.nl/
TASK 1 – PSYCHOPHARMACOLOGY THE BASIC PRINCIPLES
1. What are the specific steps of neurotransmission?
Anatomical basis of neurotransmission is neurons and the connections between
them, called synapses → sometimes also called the anatomically addressed nervous
system, a complex of ‘hard-wired’ synaptic connections between neurons. The
anatomically addressed nervous system is thus a complex wiring diagram, ferrying
electrical impulses to wherever the ‘wire’ is plugged in.
Axosomatic synapses → synapses from axon to soma.
Axoaxonic synapses → synapses that go from one neuron’s axon to another
neuron’s axon.
➔ These are asymmetric, since communication is structurally designed to be in
one direction (i.e., from axon to dendrite → axodendritic synapses).
Communication is anterograde from the axon of the first neuron to the dendrite,
soma, or axon of the second neuron.
All neurons are set up structurally to both send and receive information. Neurons
send information via an axon that forms presynaptic terminals as the axon passes by
or as the axon ends. Soma (cell body) → command centre of the nerve and contains
the nucleus of the cell.
Classic synaptic neurotransmission: stimulation of a presynaptic neuron causes
electrical impulses to be sent to its axon terminal. These electrical impulses are then
converted into chemical messengers and released to stimulate the receptors of a
postsynaptic neuron. So communication within a neuron can be electrical,
communication between neurons is chemical.
Chemical neurotransmitters are stored in small vesicles, ready for release upon firing
of the presynaptic neuron (into the synaptic cleft). The synaptic cleft reinforces the
connection between neurons.
Neurotransmission has an anatomical infrastructure, but it is fundamentally a
chemical operation. The chemically addressed nervous system forms the chemical
basis of neurotransmission: namely, how chemical signals are coded, decoded,
transduced, and sent along the way.
Six key neurotransmitter systems targeted by psychotropic drugs:
1) Serotonin;
2) Norepinephrine;
3) Dopamine;
4) Acetylcholine;
5) Glutamate;
1
, 6) GABA (γ-aminobutyric acid).
Neurotransmitters:
Neurotransmitters are endogenous chemicals that enable neurotransmission. There
are 3 classes of small-molecule neurotransmitters; amino acids, monoamines and
acetylcholine. There is only one class of large-molecule neurotransmitters;
neuropeptides. The neurotransmitters in the vast majority of fast-acting synapses in
the CNS are amino acids, the molecular building blocks of proteins. The 4 most
studied are; glutamate, glycine, aspartate, and aminobutyric acid (GABA). GABA is
synthesized by a simple modification of the structure of glutamate.
- Glutamate is the most prevalent excitatory neurotransmitter.
- GABA is the most prevalent inhibitory neurotransmitter.
Monoamine neurotransmitters have effects that tend to be more diffuse. The
network of neurons that utilize monoamine neurotransmitters are involved in the
regulation of cognitive processes such as emotion, arousal and certain types of
memory. There are five monoamine neurotransmitters; dopamine, epinephrine,
norepinephrine, serotonine and histamine. Dopamine, norepinephrine and
epinephrine are catecholamines. Catecholamines cause general physiological
changes that prepare the body for fight-flight responses. Neurons that release
norepinephrine are called noradrenergic, those that release epinephrine are called
adrenergic and dopamine are called dopaminergic. The 3 catecholamines are
synthesized from tyrosine.
- Serotonin (an indolamine) is synthesized from the amino acid tryptophan
and is involved in the sleep-wake cycle, mood, appetite, and memory and
learning. Neurons that release serotonin are called serotonergic.
o Raphaei nuclei.
Acetylcholine is a small-molecule neurotransmitter, which is a class in itself. It is the
neurotransmitter at neuromuscular junctions, at many of the synapses in the
autonomic nervous system, and at synapses in several parts of the CNS.
In general, neurotransmitters have modulating effects rather than information-
transmitting effects. The release of neurotransmitters other than glutamate and
GABA tends to activate or inhibit entire circuits of neurons that are involved in
particular brain functions.
- Acetylcholine activates the cerebral cortex and facilitates learning, but
information that is learned and remembered is transmitted by neurons that
secrete glutamate and GABA.
- Norepinephrine increases vigilance and enhances wakefulness.
- Serotonin suppresses certain categories of species-typical behaviours and
reduces the likelihood that the animal acts impulsively.
- Dopamine activates voluntary movement, but does not specify which
movements will occur. In other regions, dopamine reinforces ongoing
behaviours and makes them more likely to occur at later time.
2
,Neuromodulators are chemicals released by neurons that travel farther and more
dispersed than neurotransmitters. They modulate the activity of many neurons in a
particular part of the brain. Most neuromodulators are peptides.
Nucleus Coeruleus → brain stem nucleus where adrenaline is synthesized → one of
the most important activating neuromodulators?
Hormones are secreted by cells of endocrine glans or by cells located in various
organs, such as the stomach, intestines, kidneys and the brain. Hormones affect the
activity of cells that contain specialized receptors. Many neurons contain hormone
receptors, and hormones are able to change our behavior by changing the activity of
these neurons.
- Peptide hormones exert their effects on target cells by stimulating
metabotropic receptors located in the membrane. The second messenger that
is generated travels through the nucleus of the cell.
- Steroid hormones consist of very small fat-soluble molecules, which can be
grouped into sex hormones (secreted by ovaries and testes) and
corticosteroids (secreted by adrenal cortex). They travel through the nucleus
themselves.
3
, Drugs can influence behaviour by altering neurotransmitter activity. They have 2
different kinds of effects on synaptic transmission; they facilitate it or they inhibit it.
Once a drug has bound to a receptor, it can either serve as agonist or antagonist.
The most important and complex site of action of drugs in the nervous system is on
receptors, both presynaptic and postsynaptic. Drugs that facilitate the effects of a
neurotransmitter are said to be agonist. An agonist is a chemical that binds to a
receptor to which the neurotransmitter normally attaches and activates the same
reaction. Drugs that inhibit the effects of a neurotransmitter are called antagonists.
They block the physiological activity of another substance by binding and blocking
the active site of a receptor, but do not open the ion channel. These drugs are called
receptor blockers or direct antagonists. Some receptors have multiple binding
sites, where the neurotransmitter binds to one site, drugs to others. Binding of a
molecule with one of these alternative sites is called non-competitive binding. If this
drug prevents the ion channel from opening, it is called an indirect antagonist.
- Agonists initiate the same receptor response as the neurotransmitter, either
directly or indirectly. Indirect agonists increase the binding of
neurotransmitters at their target receptors by stimulating the release of
preventing the reuptake of neurotransmitters. An inversive agonist is an
4
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