Bath Salts and Flakka Flashcards
What do designer drugs resemble?
Amphetamine + the methylene ring feature of MDMA
What types of chemicals are designer drugs?
Cathinones, -lones, -drones
What are the sources of 3M drugs?
Khat plant
Bath salts, resemble Epsom salt crystals
What is the structure of 3M drugs?
Beta-ketonated amphetamines
What do ketones do?
Reduce lipophilicity, reduces transport across the BBB
What is 4-methylmethcathinone?
Mephedrone, the most common
What are some characteristics of the evolution of bath salts?
Synthetic and highly modified
Addition of methylenedioxy ring
Addition of pyrrolidine
Extended chains
What does pyrrolidine do?
Makes it more lipophilic so that it crosses the BBB easier and tends to be more potent
What is a third-generation flakka?
alpha-pyrrolidinovalerophone
What are some examples of 3M bath salts?
Mephedrone
MDPV
Methylone
What are the recreational effects of 3Ms?
Sympathomimetic effects, high energy
Euphoria
Arousal
What is MDPV at low doses?
A stimulant
What does MDPV do at high doses?
Induces bizarre behaviours
How do 3Ms cause euphoria?
Via elevated NAc DA
What do 3Ms increase in the NAc of rats?
DA and 5HT
What do striatal DA elevations cause?
Locomotor activity increases
What is the activity of 3Ms?
Sympathomimetic via DA, NA, 5HT increases
What are the common sympathomimetic effects of 3Ms?
Agitation, hyperthermia, tachypnea, tachycardia, hypertension, cardiac arrest
Hyperthermia leads to rhabdomyolysis which leads to kidney failure
What are the most common adverse effects of 3Ms?
Hyperthermia, hypertension, cardiac arrest, and serotonin syndrome
What are the cellular mechanisms of action of 3Ms without a pyrrolidine ring?
Similar to amphetamine
Binds DAT, SERT, NET
Enters terminals via SERT
Interact with TAAR
Leak cytoplasmic neurotransmitter stores, reverse transporter, inhibit VMAT
Mephedrone and methylone stimulate non-exocytotic release of DA, 5HT, NE
What are the cellular mechanisms of action of 3Ms with a pyrroline ring?
Similar to cocaine
Blocks transporters, does not reverse transporters
MDPV is a potent DAT/NET blocker, weaker SERT activity
What does a lower IC50 mean?
More potent
What does IC50 represent?
Represents the concentration of drug required to block 50% of uptake
How potent are bath salts compared to cocaine or amphetamines?
Just as or more potent
What does it mean to say that MDPV has a DAT/SERT of 806?
MDPV is 806x more potent at DATs compared to SERTs
What does a large carbon tail and pyrrolidine indicate?
Highest activity at DAT
What are the mechanisms of 3M reinforcement?
3M bath salts bind DAT
Mephedrone and methylone enter terminals, displace DA into synapse and reverse the DAT
MDPV does not enter terminals
What are the adverse effects of bath salts on behavior at high doses?
Violence, homicidal combative behaviour, self-mutilation, excited delirium syndrome
Panic attacks paranoia, suicidal thoughts, confusions, psychosis
What are the symptoms related to a surge in levels of dopamine, noradrenaline, and serotonin in the periphery?
Hyperthermia = involved in several deaths, leads to rhabdomyolysis and kidney failure
Tachycardia, hypertension, chest pain
Panic attacks, paranoia, suicidal thoughts, confusion, psychosis
What are the adverse effects of 3Ms?
Water intoxication which leads to hyponatremia
Increased cranial pressure causes tonsillar herniation of the cerebellum
pressure on the medulla leads to respiratory depression and cardiac arrest
What is water intoxication?
5HT causes secretion of ADH, water reabsorption occurs in the kidneys
Polydipsia evoked by hyperthermia as an attempt to cool down
Excessive sweating causes loss of Na+
What do Rhesus monkeys show in regard to MDPV and alpha-PVP?
They show higher administration for longer with MDPV and alpha-PVP compared to cocaine and meth
What do rats display when given free access to MDPV?
Escalating drug-taking behaviour
What does mephedrone cause in mice and rats?
CPP
Do bath salts have a high or low abuse potential?
A very high abuse potential
