Lecture 1 & 3: Introduction, brush up basics: Kenemans chapters 1-4
• Which two overarching classes of psychoactive substances can be discerned
based on their use?
o It can either be therapeutic or recreational
• What are the different names that are given to medications once they become
available for prescription, and what is the difference between these names?
o In the first phase only the chemical name/formula is used.
o When it is promising, it gets a codename.
o Further in development it gets a generic name, the patent holder gives the
brand name
• What is pharmacokinetics and pharmacodynamics? Describe these terms and
understand their difference. o Pharmacokinetics is about what the body does with a
substance. Things like excretion, half-life and metabolism.
o Pharmacodynamics is about what the drug does to your body, like: what is the
effect on the neurotransmitters? What are side effects? What happens inside the
body that is facilitated by the drug.
• Considered known (part of the prerequisites; self-study if unfamiliar): types of
neurotransmitters, types of receptors, common principles of neurotransmitter
synthesis (incl. precursors), degradation (incl. reuptake), principles of
communication between cells through receptors and how this influences the
chance of the postsynaptic neuron firing an action potential.
o Neurotransmitter release from the presynaptic terminal consists of a series of
intricate steps: 1) depolarization of the terminal membrane, 2) activation of
voltagegated Ca2+ channels, 3) Ca2+ entry, 4) a change in the conformation of
docking proteins, 5) fusion of the vesicle to the plasma membrane, with
subsequent release of neurotransmitter into the synaptic cleft.
Monoamines (singe amine group)
1
, • Catecholamines: DA, NE, E
o Precurser: tyrosine -> DOPA -> DA -> NE -> E
o Indolamines: 5-HT
▪ Precursor: tryptophan
• Amino acid
o Glu, GABA
▪ Precursor: glucose
• ACh
o Precursor: choline/lecithin.
• Peptides
o oxytocin, endorphines
▪ Precurser Amino Acids
• Medications have a certain indication, meaning the illness, symptoms or disorder
for which they are prescribed. In general, within which area do the indications for
psychoactive substances fall?
o Psychiatric / mental problems.
• Describe the most common mechanisms of modulation of neurotransmission
along which psychoactive substances exert their influence on the brain.
o Psychoactive substances can have an excitatory or inhibitory effect on several
mechanisms. It is possible for there to be an effect in the postsynaptic
receptors or autoreceptors, which would be done by agonists or antagonists.
It is also possible for substances to affect the reuptake signal which would
modulate the amount of neurotransmitter that stays in the presynaptic gap and
the time it remains there.
o Amount of transmitters:
▪ Synthesis (presence precursor, activity of enzymes)
▪ Uptake of transmitter in and release from vesicles
o Blocking or modulating receptor (pre/post synaptic)
o Ending influence through
▪ Reuptake
▪ Degradation (extra/intracellular)
• Many of the currently used psychoactive substances have been discovered by
serendipity, but once every so often new medications are developed on purpose
through hypothesis-driven research lines. Describe in broad terms the (pre)clinical
development phases which a new medicine has to pass before it can be made
available to patients.
1. Registration
2. Preclinical phases (animal research before humans)
3. Clinical trials (in humans)
▪ Phase 1: non-toxic, tolerable
▪ Phase 2: limited efficacy studies
▪ Phase 3: large, multi-center studies
Four phases in human drug research:
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