Lecture 10 - MDMA/LSD Flashcards
What are the physical/psychological effects of taking LSD?
Hallucinations Strong emotions - euphoria Spirituality/connectedness Pupil dilation Loss of appetite Wakefulness Altered time perception
What is the mechanism of action of LSD?
Mainly agonist of 5HT2A receptor
Also fully or partially agonises most other serotonin receptors
Also agonist of D2 dopamine receptors
Very long half life
What is the mechanism of action of psilocybin?
Prodrug - converted to psilocin
High affinity for all 5HT2 receptors
Low affinity for 5HT1a, b receptors
Shorter half life
What illnesses might hallucinogens be used to treat in the future?
Alcoholism Depression ADHD Nicotine and cocaine addiction Anxiety
What are the monoamine neurotransmitters?
Dopamine
Serotonin
Norepinephrine
Epinephrine
What transporters move the monoamines into vesicles and where in the body is each type located?
Vesicular monoamine transporters (VMAT)
VMAT1 peripherally
VMAT2 centrally and peripherally
What are the physical/psychological effects of taking MDMA?
Wakefulness and energy Euphoria Empathy and sociability Heightened senses Bruxism Hyperthermia Insomnia
What is the mechanism of action of MDMA?
Enters neurons through the monoamine transporters (SERT, DAT, NET) - causes competitive reuptake inhibition
Inactivates VMAT2 to prevent monoamine packaging into vesicles
Inactivates or reverses the monoamine transporters
Also weak agonist of 5HT1 and 5HT2 receptors
On which monoamine transporter does MDMA have the strongest affinity?
SERT
Therefore has mainly serotonergic effects
Why do different psychostimulants (cocaine, MDMA, amphetamine) have different effects?
Different selectivities for different monoamine transporters e.g. cocaine has highest preference for DAT
How can the activity of different drugs be measured?
In vitro assays (ligand binding assays and competitive binding assays)
In vivo assays (micro-dialysis)
What are the advantages of in vitro assays?
Cheap and reproducible
High throughput
Can study a single receptor or protein in isolation
Does not require animals (less cost, less ethical problems)
What are the advantages of in vivo assays?
Can measure the effects of compounds without needing to understand the mechanism
Can measured effects of drug and active metabolite
Can measure the pharmacokinetics
More physiologically relevant
Where does a majority of serotonin in the brain project from and to?
From raphe nuclei
To hypothalamus, thalamus, hippocampus, basal ganglia, cerebellum
Where does a majority of dopamine in the brain project from and to?
What is the name of this pathway?
From VTA to nucleus accumbens
Mesolimbic pathway
