Psychostimulants Flashcards
Why do users take psychostimulants?
- Alertness
- Energy
- Weight loss –> PMA, PMMA are examples of dangerous drugs which can do this
- Social disinhibition
- Pleasure
What are some drugs which are considered psychostimulants?
- Amphetamines
- MDMA/Ecstasy
- Cocaine
- Khat
What is the precursor of all synthetic amphetamines?
Tell me about their structure similarities and therefore what receptor they are able to take advantage of
- Ephedrine is the precursor of all synthetic amphetamines
- Ephedrine makes amphetamine and methamphetamine.
- All have a common structure which is a phenethylamine core so known as substituted phenethylamines.
Endogenous substituted phenethylamines are dopamine and noradrenaline. They take advantage of the dopamine and adrenaline NT systems and receptors.
Amphetamines are substituted phenethylamines – very close in structure to endogenous phenethylamines.
What type of effects do you think these drugs might have?
More alert, awake and active
Tell me what occurs when amphetamines are taken?
- Amphetamines are taken up by DAT and NET transporters.
- Once in the cytosol, they are taken up into vesicles by VMAT1/2
- They accumulate in vesicles and cause a pH change due to their amine groups.
- This degrades the pH gradient needed for VMAT1/2 to pump in neurotransmitter.
- NT accumulates in the cytosol
- Amphetamine activates intracellular TAAR1 receptors, which can cause either a reversal of the transporters, or their removal from the plasma membrane.
- Either scenario means NT is left in the synaptic cleft, leading to increased receptor activation.
* Amphetamine can also be taken up pre-synaptic terminals by DAT and NET
o Once here they are taken up by vesicular monoamine transports which pump monoamines into vesicles
o In vesicles, the amphetamine has amine groups on them which are alkali in nature and disrupt pH of vesicle
o Pumps need optimal conditions to work (temp and PH)
o The amphetamine has now disrupted pH and inhibits the pumps form working
o Leading to accumulation of monoamine in cytosol
o Either pump reverses from high –> low conc., or this transporter gets removed from membrane entirely
o In this latter scenario leads to spontaneous release of NT and leads to post-synaptic activation
What is MDMA/ ecstasy’ structure similar to?
Tell me the pharmacology of MDMA/Ecstasy
- MDMA is taken up by transporters.
- Transporters are **DAT, NET, SERT **
- Competitively taken into pre-synaptic nerve terminal like amphetamine but….
- Once in the cytosol it inhibits VMAT1/2
- Results in an accumulation of NT in the cytosol
- MDMA activates TAAR1, which again can cause transporter reversal or removal from synapse.
- Either mechanism increases NT in the synapse, and receptor activation.
What is cocaine derived from and what are the two forms it can come in?
- Derived from cocoa plant
- Cocaine can come in two forms – powder (pure) and crystals (mixed with baking soda and water and left to crystalize)
Tell me about the vaporisation temperature of the two cocaine forms?
- Called crack due to the sound it makes when heated.
- Powdered cocaine has a much higher vaporization temperature than crack – at circa 100 degrees crack vaporizes and can be inhaled. It takes a much higher temperature for powdered cocaine to vaporize, and at such a temperature the structure of the compound degrades
- Coke snorted and crack is heated in pipe, and inhaled
Tell me about the structure of cocaine
Tell me about cocaine pharmacology
Whats Khat?
What does it have a structure similar to?
How is it taken?
- Khat is a plant, whose leaves are chewed – natural
- Cathinone compounds have more recently been synthesized and become popular drugs of abuse
- Taken similarly to cocaine
Tell me about the cathinones pharmacology
What are the different dopamine pathways?
What are the effects of activating these pathways?
What are the pathways in which users want to target due to the effects they cause?
What receptors does noradrenaline target? What are these receptors?
Adrenergic receptors are metabotropic (GPCR)
What are the effects then the alpha1 adrenergic receptor is activated?
What are the effects then the alpha2 adrenergic receptor is activated?
What are the effects then the beta1 adrenergic receptor is activated?
What are the effects then the beta2 adrenergic receptor is activated?
Tell me what the adrenergic receptors couple to?
With the ‘rest and digest’ or fight or flight’ expressions, what is responsible for that?
How can snorting cocaine lead to degradation of the septum?
This effect also leads to it being used in what?
- Snorting of stimulants (most associated with cocaine), causes degradation of the septum due to the vasoconstriction which deprives the tissues of oxygen leading to tissue death
- Essentially, repeated use causes constriction of the blood vessels in the nose, and can lead to ischaemia and loss of nasal passage tissue
- Used in nasal surgery to stop bleeding (increases blood pressure?)
So… how do these drugs achieve their desired effects?
summary
Amphetamine + MDMA = competitive reuptake at pre-synaptic terminal
Cocaine + Khat = non-competitive block at pre-synaptic terminal
