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Pmcol 305 > Ectasy > Flashcards

Ectasy Flashcards

1
Q

Kollisch

A

synthesized MDMA molecule in 1912 at Merck

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2
Q

Shulgin

A

published first testing in 1960 at DOW chemicals

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3
Q

sources

A

extracted from cured plants:
- ocotea pretiosa
- sassafras albidum
- cinnamomum parthenocylon root bark

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4
Q

sassafras

A

contains ~75-85% safrole - precursor

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5
Q

ectasy

A

MDMA
hallucinogen

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6
Q

MDMA

A

methylenedioxy-methamphetamine
contains methylenedioxy ring

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7
Q

methylenedioxy ring

A

shifts stimulant effects toward mood and perceptions

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8
Q

absorption

A

ingestion - tablet/capsule
insufflation - powder (molly)
75-100mg dose

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9
Q

distribution

A

brain, lungs, liver, kidney, spleen
onset 30-45 min
TI = 14-16 (relatively safe)

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10
Q

metabolism

A

liver
80% - CYP2D6
6 hr half life
2-3 hour high

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11
Q

excretion

A

kidney
20% unchanged

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12
Q

acute effects

A

empathogen - increased empathy
entactogen - lower guard
euphoria, energy, high self-esteem
sympathomimetic

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13
Q

sympathomimetic effects

A

increased heart rate, hyperthermia, diaphoresis (increased sweating)

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14
Q

cellular mechanisms

A

5HT (1B/2) agonist

reverses 5HT transporter → TAAR phosphorylation

blocks NE and DA transporters
(10x higher affinity for 5HT)

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15
Q

5HT2B

A

Gq linked
agonist causes bruxism (jaw grinding), increased locomotion

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16
Q

blocking 5HT 2B

A

blocks MDMA-induced 5HT release in NAc and VTA

prevents MDMA-induced DA release in NAc

use antagonist / genetic deletion

17
Q

physiological mechanisms

A

increases dopamine but not very reinforcing (limited self-administration) = lower break points

increases prolactin/oxytocin → due to 5HT (bonding/empathy)

increases cortisol by 800% → feelings of excitement and happiness, higher blood glucose

18
Q

shifts brain region activation

A

towards ventral striatum (thoughtfulness)
away from amygdala (fear, rage)

19
Q

cephalopods

A

express evolutionarily conserved 5HT transporter

MDMA affects behaviour → show pro-social effects (normally asocial octopuses interact)

20
Q

molecular drug targets

A

adrenergic receptors = sympathomimetic effects, hyperthermia

histamine type 1 receptors = ACh release, EPSPs

a7 nAChR → partial agonist, increases NT release

21
Q

tolerance

A

decrease in 5HT transporter activity (+DA, NE)
decreased transporter expression
depletion of NTs

22
Q

withdrawal

A

inability to thermoregulate
lethal → ‘suicide Tuesdays’ - symptoms peak 2-3 days after use

23
Q

dependence

A

more psychological than physical
biased agonism in 5HT (2C) receptor → low addiction risk

24
Q

dangers of acute use

A

bad trips - depression, anxiety, hallucinations, paranoia
serotonin syndrome

25
Q

serotonin syndrome

A

increased heart rate, bp
muscle rigidity, hyper-diaphoresis, delirium, diarrhea, rhabdomyolysis → kidney failure, convulsion, death

26
Q

combination of MDMA + SSRIs

A

reduced effects of MDMA
competition for 5HT transporters

27
Q

combination with MAO inhibitors

A

potentiate effects of MDMA
increased NT availability

28
Q

hyperthermia

A

most common cause of overdose death
cumulative effects from 5HT, DA, NE
hyperactivity → dysregulation of temperature set points

29
Q

dysregulation of temp set points

A

D1 receptor in preoptic anterior hypothalamus
augments temp set point in vivo

MDMA increases DA release in AH

30
Q

hyponatremia

A

low Na+ in blood
hyperthermia causes large water intake
MDMA triggers ADH release

→ cerebral edema → vomiting, respiratory depression

31
Q

metabolites

A

certain metabolites cause cell death

CYP enzyme metabolism differs greatly among individuals
more or less susceptible to adverse effects, sudden death

32
Q

pharmacogenomics

A

random toxicity
variability in enzyme profiles leads to particular toxic metabolite build up

33
Q

memory and attention deficits

A

induction of apoptosis in hippocampal neurons via caspase-3 pathway (rats)

34
Q
A

Pmcol 305 (18 decks)

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