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Neuropharmacology > MDMA/LSD - monoamine oxidase transporters > Flashcards

MDMA/LSD - monoamine oxidase transporters Flashcards

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

A

cereal fungus, ergot

25
Q

main effects of LSD

A 
pupil dilation 
hallucinations
strong emotions --> euphoria
spirituality
awakefulness
loss of apetite
26
Q

binding affinity of LSD

A

very high

2.7nM –> ki is very small

27
Q

LSD has much lower binding affinity for which receptor subtype

28
Q

half life of psilocybin

A

shorter than LSD
2 hours
effects last 4-5 hours

29
Q

side effects of psilocybin

A

panic attacks

vomiting

30
Q

first pass metabolism of psilocybin

A

converted to psilocin

much more potent

31
Q

potential clinical uses for psilocybin

A

treatment of depression

alcohol addiction

32
Q

effect of blocking 5-HT2A receptors on hallucinogens

A

no effects of hallucinogens

33
Q

how many genes encode serotonin receptors

34
Q

3 presynaptic monoamine transporter

A

NAT
DAT
SERT

35
Q

feature of monoamine transporters

A

sodium coupled

36
Q

transporters to load monoamines into vesicles

A

VMAT1 - peripherally

VMAT2

37
Q

what do psychostimulants target

A

monoamine transporters

38
Q

effects of MDMA

A 
increased wakefulness, energy
euphoria
increased empathy, sociability
increased senses
bruxism (teeth clenching/grinding)
elevated HR, BP
addictive
39
Q

pharmacology of MDMA

A

enters via monoamine transporters e.g. SERTs
inactivates VMATs
reverses SERTs –> dumps all the serotonin back into the synaptic cleft

40
Q

clinical use of monoamine transporter antagonists

A

treatment of substance abuse

41
Q

clinical use of monoamine transporter agonists

A

treatment of depression, ADHD, anxiety

42
Q

how many different genes for dopamine receptors

43
Q

structure of all dopamine receptors

44
Q

D1-like dopamine receptors

A

D1 and D5

Gs signalling

45
Q

D2-like dopamine receptors

A

D2, D3, D4

Gi/o signalling

46
Q

important dopamine target for antipsychotics

A

D2-like dopamine receptors

47
Q

different levels of measuring a drugs avtivity

A

from molecular level, to tissue, to an entire animal to clinical trials etc.

48
Q

in vitro assay to measure drug activity

A

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
Q

advantages of in vitro assays

A

cheap
reproducible
high throughput
can study single protein/receptor in isolation

50
Q

disadvantages of in vitro assays

A

recombinant receptors do not always behave in the same way
cant measure active metabolites
cant measure pharmacokinetics e.g. how quickly drugs cleared

51
Q

in vivo assay

A

measure effect of compound using whole animal

52
Q

method of in vivo microdialysis

A 
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
Q

advantages of in vivo assays

A

allows measurement of effects without knowing mechanism
can measure pharmacokinetics
more physiological relevance

54
Q

disadvantages of in vivo assays

A

doesnt determine mechanism
low throughput
uses whole animal (cost/ethics)

55
Q

where does serotonin come from

A

raphe nuclei in the brain stem

projects throughout entire brain

56
Q

where do norepinephrine projections arise from

A

locus coeruleus

57
Q

potential neurotransmitter co-release mechanisms

A

more than one NT in the same vesicle
different vesicles releasing different NT
different pre-synaptic boutons

58
Q

many neurons release both a classical NT as well as a

A

neuropeptide

e.g. somatostatin, ATP

Neuropharmacology (14 decks)

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