Bath salts Flashcards
designer drugs
derived from cathinone chemicals
evolving classes of stimulants
resemble AMPH + methylene ring (seen in MDMA)
cathinones
-lones and -drones
beta-ketonated amphetamines
bath salts
sourced from khat plant
resemble bath salts, epsom salt crystals
chemical structure
ketone reduces lipophilicity → reduces transport across BBB
mephedrone
first semi-synthetic cathinone
4-methylmethcathinone
most common
meth + methyl
chemical evolution
synthetic; highly modified
- addition of methylenedioxy ring
- addition of pyrrolidine
methylenedioxy ring
two Os + C in between
like MDMA
two Os = similar to E, NE NTs
added to methylone
pyrrolidine
4C + N
makes molecule more lipophilic = more easily crosses BBB
more potent
added to MDPV
3rd generation bath salts
a-PVP, a-PBP, a-PPP
have pyrrolidine, no methylenedioxy ring
extended chains on gamma carbon
PPP = methyl
PBP = ethyl
PVP = propyl
3M bath salts
mephedrone
methylone
MDPV
recreational effects of 3Ms
sympathomimetic effects
high energy
euphoria
arousal
methylone
meth + methylenedioxy ring
MDPV
methylone + pyrrolidine, extended chain
stimulant at low doses
bizarre behaviours at higher doses
physiological mechanisms of 3Ms
elevated NAc DA = euphoria
increased DA and 5HT in NAc
striatal DA elevations = increased locomotor activity
increased DA, NE, 5HT
sympathomimetic effects
agitation, hyperthermia, tachypnea, tachycardia, hypertension, cardiac arrest
common adverse effects
hyperthermia
hypertension
cardiac arrest
serotonin syndrome
hyperthermia
can lead to rhabdomyolysis (kidney failure)
cellular mechanisms (without pyrrolidine ring)
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
cellular mechanisms (with pyrroidine ring)
similar to cocaine (MDPV)
potent DAT/NET blocker (weaker SERT activity)
blocks transporters - does not reverse transporters
transporter assays
IC50
concentration of drug required to block 50% of uptake
lower IC50 = more potent (prefers to bind that transporter)
DAT/SERT ratio
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
bath salt potency
more potent than cocaine, AMPH
structure-activity relationship
larger carbon tail + pyrrolidine = highest activity at DAT
MDPV has most activity
a-PPP has least
mechanism of reinforcement
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
DAT
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
behavioural adverse effects
violence, homicidal combative behaviour, self-mutilation, excited delirium syndrome
panic attacks, paranoia, suicidal thoughts, confusion, psychosis
especially MDPV
fatal NT levels
surge in DA, NE, and 5HT levels in periphery
cause:
- hyperthermia
- tachycardia, hypertension, chest pain
- panic attacks, paranoia, suicidal thoughts, confusion, psychosis
hyponatremia
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
dependence (self-administration, drug-taking behaviour, CPP)
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
