Bath Salts and Flakka

Question 1

What do designer drugs resemble?

Answer 1

Amphetamine + the methylene ring feature of MDMA

Question 2

What types of chemicals are designer drugs?

Answer 2

Cathinones, -lones, -drones

Question 3

What are the sources of 3M drugs?

Answer 3

Khat plant
Bath salts, resemble Epsom salt crystals

Question 4

What is the structure of 3M drugs?

Answer 4

Beta-ketonated amphetamines

Question 5

What do ketones do?

Answer 5

Reduce lipophilicity, reduces transport across the BBB

Question 6

What is 4-methylmethcathinone?

Answer 6

Mephedrone, the most common

Question 7

What are some characteristics of the evolution of bath salts?

Answer 7

Synthetic and highly modified
Addition of methylenedioxy ring
Addition of pyrrolidine
Extended chains

Question 8

What does pyrrolidine do?

Answer 8

Makes it more lipophilic so that it crosses the BBB easier and tends to be more potent

Question 9

What is a third-generation flakka?

Answer 9

alpha-pyrrolidinovalerophone

Question 10

What are some examples of 3M bath salts?

Answer 10

Mephedrone
MDPV
Methylone

Question 11

What are the recreational effects of 3Ms?

Answer 11

Sympathomimetic effects, high energy
Euphoria
Arousal

Question 12

What is MDPV at low doses?

Answer 12

A stimulant

Question 13

What does MDPV do at high doses?

Answer 13

Induces bizarre behaviours

Question 14

How do 3Ms cause euphoria?

Answer 14

Via elevated NAc DA

Question 15

What do 3Ms increase in the NAc of rats?

Answer 15

DA and 5HT

Question 16

What do striatal DA elevations cause?

Answer 16

Locomotor activity increases

Question 17

What is the activity of 3Ms?

Answer 17

Sympathomimetic via DA, NA, 5HT increases

Question 18

What are the common sympathomimetic effects of 3Ms?

Answer 18

Agitation, hyperthermia, tachypnea, tachycardia, hypertension, cardiac arrest
Hyperthermia leads to rhabdomyolysis which leads to kidney failure

Question 19

What are the most common adverse effects of 3Ms?

Answer 19

Hyperthermia, hypertension, cardiac arrest, and serotonin syndrome

Question 20

What are the cellular mechanisms of action of 3Ms without a pyrrolidine ring?

Answer 20

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

Question 21

What are the cellular mechanisms of action of 3Ms with a pyrroline ring?

Answer 21

Similar to cocaine
Blocks transporters, does not reverse transporters
MDPV is a potent DAT/NET blocker, weaker SERT activity

Question 22

What does a lower IC50 mean?

Answer 22

More potent

Question 23

What does IC50 represent?

Answer 23

Represents the concentration of drug required to block 50% of uptake

Question 24

How potent are bath salts compared to cocaine or amphetamines?

Answer 24

Just as or more potent

Question 25

What does it mean to say that MDPV has a DAT/SERT of 806?

Answer 25

MDPV is 806x more potent at DATs compared to SERTs

Question 26

What does a large carbon tail and pyrrolidine indicate?

Answer 26

Highest activity at DAT

Question 27

What are the mechanisms of 3M reinforcement?

Answer 27

3M bath salts bind DAT Mephedrone and methylone enter terminals, displace DA into synapse and reverse the DAT MDPV does not enter terminals

Question 28

What are the adverse effects of bath salts on behavior at high doses?

Answer 28

Violence, homicidal combative behaviour, self-mutilation, excited delirium syndrome Panic attacks paranoia, suicidal thoughts, confusions, psychosis

Question 29

What are the symptoms related to a surge in levels of dopamine, noradrenaline, and serotonin in the periphery?

Answer 29

Hyperthermia = involved in several deaths, leads to rhabdomyolysis and kidney failure Tachycardia, hypertension, chest pain Panic attacks, paranoia, suicidal thoughts, confusion, psychosis

Question 30

What are the adverse effects of 3Ms?

Answer 30

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

Question 31

What is water intoxication?

Answer 31

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+

Question 32

What do Rhesus monkeys show in regard to MDPV and alpha-PVP?

Answer 32

They show higher administration for longer with MDPV and alpha-PVP compared to cocaine and meth

Question 33

What do rats display when given free access to MDPV?

Answer 33

Escalating drug-taking behaviour

Question 34

What does mephedrone cause in mice and rats?

Answer 34

CPP

Question 35

Do bath salts have a high or low abuse potential?

Answer 35

A very high abuse potential