Bath salts

Question 1

designer drugs

Answer 1

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

Question 2

cathinones

Answer 2

-lones and -drones
beta-ketonated amphetamines

Question 3

bath salts

Answer 3

sourced from khat plant
resemble bath salts, epsom salt crystals

Question 4

chemical structure

Answer 4

ketone reduces lipophilicity → reduces transport across BBB

Question 5

mephedrone

Answer 5

first semi-synthetic cathinone
4-methylmethcathinone
most common

meth + methyl

Question 6

chemical evolution

Answer 6

synthetic; highly modified

• addition of methylenedioxy ring
• addition of pyrrolidine

Question 7

methylenedioxy ring

Answer 7

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

added to methylone

Question 8

pyrrolidine

Answer 8

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

added to MDPV

Question 9

3rd generation bath salts

Answer 9

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

Question 10

3M bath salts

Answer 10

mephedrone
methylone
MDPV

Question 11

recreational effects of 3Ms

Answer 11

sympathomimetic effects
high energy
euphoria
arousal

Question 12

methylone

Answer 12

meth + methylenedioxy ring

Question 13

MDPV

Answer 13

methylone + pyrrolidine, extended chain

stimulant at low doses
bizarre behaviours at higher doses

Question 14

physiological mechanisms of 3Ms

Answer 14

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

Question 15

increased DA, NE, 5HT

Answer 15

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

Question 16

common adverse effects

Answer 16

hyperthermia
hypertension
cardiac arrest
serotonin syndrome

Question 17

hyperthermia

Answer 17

can lead to rhabdomyolysis (kidney failure)

Question 18

cellular mechanisms (without pyrrolidine ring)

Answer 18

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

Question 19

cellular mechanisms (with pyrroidine ring)

Answer 19

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

blocks transporters - does not reverse transporters

Question 20

transporter assays

Question 21

IC50

Answer 21

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

Question 22

DAT/SERT ratio

Answer 22

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

Question 23

bath salt potency

Answer 23

more potent than cocaine, AMPH

Question 24

structure-activity relationship

Answer 24

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

Question 25

mechanism of reinforcement

Answer 25

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

Question 26

DAT

Answer 26

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

Question 27

behavioural adverse effects

Answer 27

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

Question 28

fatal NT levels

Answer 28

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

Question 29

hyponatremia

Answer 29

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

Question 30

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

Answer 30

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