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Neuropharmacology > MDMA/LSD - monoamine oxidase transporters > Flashcards

MDMA/LSD - monoamine oxidase transporters Flashcards

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1
Q

5-HT

A

serotonin

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2
Q

most 5-HT receptors are

A

metabotropic/GPCRs

only 5HT3 ionotropic

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3
Q

what is different about 5-HT3 receptor

A

ionotropic

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4
Q

activation of Gq coupled 5HT receptors

A

leads to hydrolysis of membrane phosphoinositides
increased DAG and IP3
activation of PKC
increased intracellular Ca2+

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5
Q

activation of Gs coupled 5HT receptors

A

stimulates adenyl cyclase
increased cAMP
activation of PKA

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6
Q

activation of Gi/o coupled 5HT receptors

A

inhibition of adenyl cyclase

decreased cAMP

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7
Q

what are 5HT3 receptors important for

A

mediation of fast excitatory neurotransmission

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8
Q

what does LSD stand for

A

lysergic acid diethylamide

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9
Q

LSD simple pharmacology

A

agonist of many 5HT receptors and also some dopamine receptors

most important = agonist of 5-HT2A

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10
Q

half life of LSD

A

long
175 minutes
effects last for 12 hours

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11
Q

psychedelic in magic mushrooms

A

psilocybin

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12
Q

3 monoamine neurotransmitters

A

serotonin
dopamine
norepinephrine

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13
Q

most common psychostimulant

A

MDMA/ecstacy

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14
Q

2 other psychostimulants

A

cocaine

amphetamine

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15
Q

which 5-HT receptors use Gq signalling

A

5-HT2A
5-HT2B
5-HT2C

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16
Q

where are 5-HT2A receptors found

A

dendrites in cortical areas

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17
Q

when are 5-HT2B important

A

during development

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18
Q

where are 5-HT2C receptors found

A

mesolimbic dopaminergic pathway (VTA) and amygdulla

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19
Q

which 5-HT receptors couple via Gas

A

5-HT4
5-HT6
5-HT7

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20
Q

where are 5-HT4 receptors found

A

substantia nigra
hippocampus
basal ganglia
cortex

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21
Q

where are 5-HT6 receptors found

A

almost exclusively in CNS

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22
Q

where are 5-HT7 receptors found

A

hypothalamus
thalamus
cortex
hippocampus

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23
Q

which 5-HT receptors couple via Gi/o

A

5-HT1A,B,D,E,F

5-HT5A,B

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24
Q

LSD derived from

Study These Flashcards
A

cereal fungus, ergot

25
main effects of LSD
``` pupil dilation hallucinations strong emotions --> euphoria spirituality awakefulness loss of apetite ```
26
binding affinity of LSD
very high | 2.7nM --> ki is very small
27
LSD has much lower binding affinity for which receptor subtype
5-HT6
28
half life of psilocybin
shorter than LSD 2 hours effects last 4-5 hours
29
side effects of psilocybin
panic attacks | vomiting
30
first pass metabolism of psilocybin
converted to psilocin | much more potent
31
potential clinical uses for psilocybin
treatment of depression | alcohol addiction
32
effect of blocking 5-HT2A receptors on hallucinogens
no effects of hallucinogens
33
how many genes encode serotonin receptors
14
34
3 presynaptic monoamine transporter
NAT DAT SERT
35
feature of monoamine transporters
sodium coupled
36
transporters to load monoamines into vesicles
VMAT1 - peripherally | VMAT2
37
what do psychostimulants target
monoamine transporters
38
effects of MDMA
``` increased wakefulness, energy euphoria increased empathy, sociability increased senses bruxism (teeth clenching/grinding) elevated HR, BP addictive ```
39
pharmacology of MDMA
enters via monoamine transporters e.g. SERTs inactivates VMATs reverses SERTs --> dumps all the serotonin back into the synaptic cleft
40
clinical use of monoamine transporter antagonists
treatment of substance abuse
41
clinical use of monoamine transporter agonists
treatment of depression, ADHD, anxiety
42
how many different genes for dopamine receptors
5
43
structure of all dopamine receptors
GPCR
44
D1-like dopamine receptors
D1 and D5 | Gs signalling
45
D2-like dopamine receptors
D2, D3, D4 | Gi/o signalling
46
important dopamine target for antipsychotics
D2-like dopamine receptors
47
different levels of measuring a drugs avtivity
from molecular level, to tissue, to an entire animal to clinical trials etc.
48
in vitro assay to measure drug activity
radioactive labelled substrate for the receptor filter through and wash and measure residual radioactivity add other drug and see how much it displaces the radioactive-labelled drug
49
advantages of in vitro assays
cheap reproducible high throughput can study single protein/receptor in isolation
50
disadvantages of in vitro assays
recombinant receptors do not always behave in the same way cant measure active metabolites cant measure pharmacokinetics e.g. how quickly drugs cleared
51
in vivo assay
measure effect of compound using whole animal
52
method of in vivo microdialysis
``` give little mouse MDMA stick probe in its brain pump perfusate into probe semi permeable membrane allows drug to pass into measure amount of drug every 20 mins ```
53
advantages of in vivo assays
allows measurement of effects without knowing mechanism can measure pharmacokinetics more physiological relevance
54
disadvantages of in vivo assays
doesnt determine mechanism low throughput uses whole animal (cost/ethics)
55
where does serotonin come from
raphe nuclei in the brain stem | projects throughout entire brain
56
where do norepinephrine projections arise from
locus coeruleus
57
potential neurotransmitter co-release mechanisms
more than one NT in the same vesicle different vesicles releasing different NT different pre-synaptic boutons
58
many neurons release both a classical NT as well as a
neuropeptide | e.g. somatostatin, ATP

Neuropharmacology (14 decks)

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