Bath salts and plant food Flashcards
What are bath salts?
bath salts are a family of designer stimulant drugs that have become popular alternatives to traditional drugs like cocaine and MDMA
the types in circulation frequently change over time as one becomes illegal, others get invented to avoid being illegal
most have reputation for being dangerous drugs that can harm or kill the user
no clinical testing done of them
since 2010, there has been 100 deaths associated with MDPV use alone
they are easy to obtain and cheap and for the most part, legal until the government catches up to them
What determines whether a drug is illegal or not?
often legality of drugs is based on specific chemical structure
therefore if structure is changed sufficiently, it may no longer be considered ‘illegal’
what are ‘designer’ drugs? what are some dangers associated with designer drugs?
designer drugs are ones that are always changing the structure to not catch up with the law
dangers associated with designer drugs:
- no acute animal or human testing
- no long term testing
- no idea of the LD50 (value of drug dose required to kill half the tested population)
- the right doses are found by trial and error (i.e. someone takes X amount and dies)
- interesting side effects: a contaminant of a designer opioid drug caused parikinsonism in its users, mow used as investigative tool to induce Parkinsons in animal models
what are synthetic cathinones and why did they appear?
caxhinone is a naturally occurring drug found in a plant called KHAT
KHAT was made illegal in many countries due to hospitalization of many users so people started making KHAT derivatives (a synthetic cathininone) early 2000
it appeared available online for purchase in 2007
what was one of the first reported components of bath salts?
Mephedrone was one the first reported components of bath salts = 4-methylmethcathinone
What is another name for cathinone and its derivatives? what are their structural properties?
cathinone and its derivatives are known as beta detonated amphetamines
ketone group makes it more polar and slower than AMPH to cross the BBB (exception is MDPV and derivatives because of their tertiary amino group)
mephedrone is a semi synthetic derived from caxhinone
some cathinones are structurally similar to amphetamines while others are similar to methamphetamines
Mehylone and MDPV are similar to MDMA
What are some cathinone derivates of bath salts?
ephedrine, methylone, MDPV and others
in 2013 what were the top 3 drugs of choice of bath salts?
- alpha-PVP
- Methylone
- MDPV
what was the drug of choice in 2014?
- alpha-PVP
- ethylone
- methylone
and MDVP moved down 3 spots
shows that drugs can change rapidly year to year with new creations
How are bath salts administered?
most common routes are snorting AND injection at the same time through a process called KEYING AND PARACHUTING/BOMBING
keying involves dipping keys into powder and snorting
then parachuting involves wrapping powder in cigarette paper and swallowing it
these two combined provide the rapid onset of sniffing and the delayed onset of injestion for prolonged effects
MDPV, has the high lipophilicity can produce effects with very small doses (as little as 5mg) but tends to have a shorter duration
What are the 3M’s?
MEPHEDRONE, METHYLONE AND MDPV
what are some of the effects of the 3M’s?
all can produce sympathetic excitation by increasing dopamine and noradrenaline levels
- can produce death from “excited delirium”
which is excess agitation, cardiovascular excitation and death
- linked to ability to increase NORE levels by blocking its transporter
also blocks dopamine transporter
MDPV and its derivatives seem to be stimulants at low doses but produce horrible behaviours at high doses
what is the biphasic effect?
MDPV and derivatives act like other cathinones at low doses but at high doses you get bizarre behaviours like self mutilation
In what ways do cathinones such as MDPV share behavioural similarities with AMPH?
Mice were trained to press a lever to receive direct electrical stimulation to reward pathway
drugs of abuse will increase this behaviour at low frequencies of sitmulation
methAMPH and MDPV had the same results
in both the animal works harder the less of the drug
what is alpha-PVP or Flakka?
Flakka is a second generation bath salt and the new “most dangerous thing ever”
also known as gravel
- very cheap to use $5
introduced when first generation drugs were made illegal
linked to a lot of deaths considering their recent introduction
other chemicals in this family include alpha-PPP and alpha-PBP and they differ from alpha-PVP by the length of their carbon tails
what are the properties of flaka and alpha-PVP derivatives?
alpha-PVP Is a derivative of the potent MDPV and its just the removal of the methyelenedioxy ring in MDPV but kept the teritary amine group to cross the bilayer faster
the tertiary nitrogen of the pyrrolidine ring allows them to cross lipids more easily than other cathinones
therefore they tend to be more potent than other cathinones that do lack this group
removal of one methyl group of alpha-PVP gives rise to alpha-PBP and removal of one methyl group from alpha-PBP is alpha-PPP
What is the mechanism of action of MDPV and other pyrrolidine ring derivatives?
MDPV and other pyrrolidine ring derivatives like alpha-PVP have similar actions to cocaine
- MDPV is a potent transporter blocker but does not seem to reverse transporter flux
- also, theres evidence that flakka and its anologues do not induce reversal of transporters
What is the mechanism of action of Cathinones without pyrrolidine ring?
cathinones without pyrrolidine ring tend to have similar mechanism of action to the amphetamines –> bind to and inhibit transporters for dopamine, serotonin and NORE
(includes methcathinone and MEPHEDRONE)
transported into the neuron by serotonin transporter (SERT) and other transporters
releases cytoplasmic stores of NT via reversal of transporters and inhibition of VMAT-dependent NT uptake into vesicles
How are the effects on transporters measured?
transporters are involved because drugs will inhibit transport of NT’s into nerve terminals by interacting with the transporters
- use of synaptosome preparation –> grinding up brain tissue and nerve endings are sheared off and spontaneously form into sealed vesicle
- transporters are still active and can accumulate neruostramsitter
- and from this we can see how drugs affect this accumulation
How do we measure NT transport?
if we add radioactive neurotransmitter to synaptosomes, we can measure how much they accumulate and make a graph out of this to show normal accumulation
- i.e. as dopamine concentration rises, so does the amount of dopamine in the synaptosome, we use this and add a drug to see how drugs affect the curve
What if we measure dopamine accumulation In the presence of the drug?
First we look at MAX dopamine that could enter the synaptosome at dopamine = 100%
then we add the drug and see what happens to the overall dopamine inside the synaptosome…
we can see that the transporters are getting affected by drug because they are binding to it and letting less dopamine into the synaptosome and more floating around the outside
what is the IC50 concentration of the drug concentration v. accumulation curve?
it is the concentration of the drug that causes 50% decrease in uptake
The more concentration it takes to reach IC50 means that you need more of the drug to get less than 50% of the dopamine within the synaptosome and the drug is not as potent
if the graph is more the right = drug is not as potent
lower numbers = higher potency
higher number = lower potency
Which drugs (cocaine, AMPH, MDPV and alpha-PVP) are more potent at Dopamine transporter? (need less)
MDVP (4.1) and alpha-pvp
cocaine and amphetamine have a higher number so they are less potent
Which drugs (cocaine, AMPH, MDPV and alpha-PVP) are more potent at SERT transporter? (need less)
cocaine has the least potency at this receptor at 313 while alpha PVP virtually does not even affect SERT
