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Pmcol 305 > Bath salts > Flashcards

Bath salts Flashcards

1
Q

designer drugs

A

derived from cathinone chemicals
evolving classes of stimulants
resemble AMPH + methylene ring (seen in MDMA)

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2
Q

cathinones

A

-lones and -drones
beta-ketonated amphetamines

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3
Q

bath salts

A

sourced from khat plant
resemble bath salts, epsom salt crystals

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4
Q

chemical structure

A

ketone reduces lipophilicity → reduces transport across BBB

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5
Q

mephedrone

A

first semi-synthetic cathinone
4-methylmethcathinone
most common

meth + methyl

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6
Q

chemical evolution

A

synthetic; highly modified

  • addition of methylenedioxy ring
  • addition of pyrrolidine
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7
Q

methylenedioxy ring

A

two Os + C in between
like MDMA
two Os = similar to E, NE NTs

added to methylone

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8
Q

pyrrolidine

A

4C + N
makes molecule more lipophilic = more easily crosses BBB
more potent

added to MDPV

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9
Q

3rd generation bath salts

A

a-PVP, a-PBP, a-PPP
have pyrrolidine, no methylenedioxy ring
extended chains on gamma carbon
PPP = methyl
PBP = ethyl
PVP = propyl

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10
Q

3M bath salts

A

mephedrone
methylone
MDPV

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11
Q

recreational effects of 3Ms

A

sympathomimetic effects
high energy
euphoria
arousal

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12
Q

methylone

A

meth + methylenedioxy ring

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13
Q

MDPV

A

methylone + pyrrolidine, extended chain

stimulant at low doses
bizarre behaviours at higher doses

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14
Q

physiological mechanisms of 3Ms

A

elevated NAc DA = euphoria
increased DA and 5HT in NAc
striatal DA elevations = increased locomotor activity

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15
Q

increased DA, NE, 5HT

A

sympathomimetic effects
agitation, hyperthermia, tachypnea, tachycardia, hypertension, cardiac arrest

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16
Q

common adverse effects

A

hyperthermia
hypertension
cardiac arrest
serotonin syndrome

17
Q

hyperthermia

A

can lead to rhabdomyolysis (kidney failure)

18
Q

cellular mechanisms (without pyrrolidine ring)

A

similar to AMPH (mephedrone + methylone)
stimulate non-exocytotic release of DA, 5HT

bind DAT, SERT, NET
enter terminals via SERT
interact with TAAR
leak cytoplasmic NT stores, reverse transporter, inhibit VMAT

19
Q

cellular mechanisms (with pyrroidine ring)

A

similar to cocaine (MDPV)
potent DAT/NET blocker (weaker SERT activity)

blocks transporters - does not reverse transporters

20
Q

transporter assays

A
21
Q

IC50

A

concentration of drug required to block 50% of uptake
lower IC50 = more potent (prefers to bind that transporter)

22
Q

DAT/SERT ratio

A

describes differences in activity
SERT / DAT

higher number = favours DAT
MDPV is 806x more potent at DATs

closer to 1 = equal effects on DAT and SERT

23
Q

bath salt potency

A

more potent than cocaine, AMPH

24
Q

structure-activity relationship

A

larger carbon tail + pyrrolidine = highest activity at DAT
MDPV has most activity
a-PPP has least

25
Q

mechanism of reinforcement

A

all 3Ms show spikes in DA followed by a drop (in NAc)
mephedrone shows highest spike in both DA and 5HT; methylone shows smaller spikes in both
MDVP = best stimulant - only DA, no 5HT activity

26
Q

DAT

A

3Ms bind DAT
mephedrone and methylone enter terminals, displace DA into synapse and reverse DAT
MDPV does not enter terminals, only blocks DA

reinforcement mechanism

27
Q

behavioural adverse effects

A

violence, homicidal combative behaviour, self-mutilation, excited delirium syndrome
panic attacks, paranoia, suicidal thoughts, confusion, psychosis

especially MDPV

28
Q

fatal NT levels

A

surge in DA, NE, and 5HT levels in periphery
cause:
- hyperthermia
- tachycardia, hypertension, chest pain
- panic attacks, paranoia, suicidal thoughts, confusion, psychosis

29
Q

hyponatremia

A

water intoxication

5HT causes secretion of ADH → kidneys reabsorb water
hyperthermia + high metabolism cause polydipsia (thirst)
excessive sweating = loss of Na+

leads to increased cranial pressure → tonsilar herniation of cerebellum → pressure on medulla = respiratory depression, cardiac arrest

30
Q

dependence (self-administration, drug-taking behaviour, CPP)

A

rhesus monkeys show higher self-administration for longer with MDPV and a-PVP compared to cocaine + meth

rats show increased drug-taking behaviour with free access to MDPV

mephedrone causes CPP in mice and rats

= high abuse potential

31
Q
A

Pmcol 305 (18 decks)

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