2 - hallucinogens Flashcards
what are three monoamine transmitters
serotonin, norepinephrine, dopamine
what is the role of the mooamines
regulate mood, appetite, sleep, cognition, perception, arousal
how do drugs affect the monoamines
increasing release, blocking reuptake, inhibit metabolism, or activate receptor
how many types of serotonin receptors
7 subtypes
what kind of receptors for norepinephrine
alpha and beta adrenergic receptors
what kind of receptors for dopamine
D1 and D2
what kind of receptors are 5HT, NE, domaine?
they are all GPCRs
except for 5HT-3
what kind of receptor is 5HT-3
a ligand gated ion channel
how many type of G protein receptors are there,
what are they called
Gi (inhibitory)
Gs (excitatory)
Gq (modulatory)
how are the monoamines metabolized
by monoamine oxidases (MAO)
how do the MAO work
catalyze the oxidation of the monoamines
how do MAOI work
they block the action of MAO (block monoamine oxidation)
what are the 3 monoamine transporters
NET
DAT
SERT
what do the NE DAT and SERT do
clear synaptic neurotransmitters by actively transporting the them into the cytosol
what is VMAT stand for
vesicular monoaminergic transporter
what does VMAT do
pump cytosolic neurotransmitters into vesicles to be released back into the synapse after AP
where are DAT, SERT and NET found
on the plasma membrane
where are VMATs found
on the membrane of vesicles
where does LSD originate from
ergot, fungus from rye
what are the effects of LSD
dilated pupils, increased heart rate, increased BP, hallucinations, some enlightenment
what are the adverse psychiatric effects of LSD
anxiety, paranoia and delusions are possible
what is hallucinogen persisting perception disorder
when distressing visual hallucinations that appear following drug use
how many receptor targets of LSD
what is the most common
over 50, with several 5-HT receptors
what receptor mediates hallucinogenic effects
5-HT2a
how does LSD interact with the 5-HT2a receptors
LSD has a high affinity and is a partial agonist at the 5-HT2a receptors
are all 5-HT2a agonists hallucinogenic
why or why not
no
because of biased agonism (LSD activates phospholipase A2, serotonin activates phospholipase C)
how do we know 5-HT2a mediates the hallucinations
tests in mice, they have head bobs
what does biased agonist of the 5-HT2a cause
different expression of transcription factors (Thats why some are hallucinogenic and others arent)
can you build a tolerance to LSD
yes
lasts several days
how does LSD tolerance happen
downregulation of 5-HT2 receptors (not other 5-HT tho)
what is cross tolerance
tolerance of multiple drugs that act at serotonin receptors (LSD, DMT, psilocybin)
what is the structure of indolamines
benzene + 5 membered pyrrole + amine
what structure are indolamines similar to
serotonin
what are the side effects of psilocybin
euphoria, hallucinations, change in perception of time
what are the adverse reactions of psilocybin
nausea, panic attacks
can you overdose from psilocybin
no
how is psilocybin handled in the body
psilocybin (prodrug) is dephosphorylated into psilocin
what kind of effects of psulocin have at which receptors
partial agonist at 5HT receptors. high affinity for 5HT-2c and 5-HT2b receptors, low affinity for 5-HT2a receptors
how does psilocybin have hallucinations
5-HT2a
what is DMT structurally similar to
tryptamine
what is the only hallucinogen that is naturally produced in the mammalian brain
DMT
how does DMT affect receptors
partial agonist at 5-HT receptors
how does DMT cause hallucinations
5-HT2a
what are the roles of phenethylamines in the body
modulate the monoamine system
what are types of ways phenethylamines affect the body
CNS stimulates (amphetamine, MDMA)
Hallucinogenics (MDMA)
antidepressants
overall –>wide variety!!
what does mescaline come from
peyote cactus
naturally occurring!
what is mescaline synthesized from
tyrosine
which receptors do mescnaline bind to and what affinity
5-HT2A receptors with high affinity
is mescaline addictive
not really
what are the side effects (good)of MDMA
increased energy, empathy, pleasure, hallucinations
what are the bad side effects of MDMA
memory impairment, paranoia, difficulty sleepy, teeth grinding, blurred vision, sweating, tachycardia, addiction
what causes MDMA related deaths
increased body temperature and dehydration
what is MDMA similar in structure to
the monoamines
what is mescaline similar in structure to
the monoamines
how does MDMA cause the hallucinogenic effects
5HT-2A partial agonist
what is efflux
reversing the direction of transport, allows amines to flow backwards through plasma membrane transporters (exits the cell)
what does efflux cause to neurotransmitters
increased synaptic concentration of neurotransmitters
how does MDMA affect efflux
it acts as a substrate for monoaminergic transporters, where it induces efflux
affects TRANSPORTERS not receptors
what does MDMA bind to
SERT (10x selectivity for SERT than NET or DAT)
what does amphetamines do to CNS
stimulates
how do amphetamines cause hallucinations
they dont lol
what are the effects of amphetamines
euphoria, fatigue resistance, improved cognitive control, addiction, psychosis
what receptors does amphetamines affect
and how
DAT and NET more than SERT
inhibits monoamine transporter through efflux (like MDMA)
why are amphetamines less hallucinogenic than MDMA
MDMA affects SERT (which affects the 5HT-2A receptors) while amphetamines are more selective for NET and DAT
what is methylphenidate
ritalin, used to treat ADHD
what are the effects of methylphenidate
improved alertness and concentration, no hallucination, safe and widely prescribed
which receptors does methylphenidate affect
NE and DAT efflux
why does amphetamine have a higher risk of addiction than methylphenidate
methylphenidate gets into the system slower, slow rate of onset, slow rate of offset, not a “rush” associated with the drug
what does small Ki
The smaller the Ki, the greater the binding affinity and the smaller amount of medication needed in order to inhibit the activity of that enzyme.
