Week 6 - Psychostimulants Flashcards
What is another name for psychostimulants?
sympathomimetics - drugs that increase sympathetic nervous system activity.
What are some examples of psychostimulants?
amphetamines (Adderall), methylphenidate (Ritalin), cathinone (bath salts), cocaine, nicotine, caffeine
What is ephedrine’s related psychostimulant and where are the two psychostimulants derived from?
- pseudoephedrine
2. the plant Ephedra
What is amphetamine’s related psychostimulant and where are these two psychostimulants derived from?
- Methamphetamine
2. Lab synthesis from ephedrine and pseudoephedrine
What is methylphenidate derived from?
Derived from lab synthesis
What is cathinone derived from?
Derived from the khat plant
What psychostimulants are derived from cathinone?
Mephedrone, methylone, and methylenedioxypyrovalerone.
What is the preferred route of administration?
Depends…
For rapid absorption inhalation, IV, insufflation are used (in recreational situations).
However for therapeutic uses, a slower absorption rate is preferred, so oral routes are probably preferred.
Why is cocaine faster when inhaled rather than administered through an IV?
Cocaine that is taken in intraveneously is in its salt form while cocaine that is heated up for inhalation is in its freebase form hence inhaled cocaine reaches its peak quicker.
What is methamphetamine metabolized into, in the liver?
Methamphetamine is metabolized into amphetamine. *Psychostimulant effects by both methamphetamine and amphetamine.
What active metabolite is produced from cathinone metabolism in the liver?
norephedrine (d optical isomer of pseudoephedrine). *Psychostimulant effects by both cathinone and pseudoephedrine.
What drug is produced when cocaine is administered with alcohol?
Cocaethylene. *polydrug use - the use of multiple substances, normally with the intention of achieving a specific effect (more chance of abuse)
What does the elimination rate have to do with how abused a psychostimulant may be?
Psychostimulants with faster elimination rates are more likely to be abused because the effects of a psychostimulant with faster elimination rates won’t last as long. This is why cocaine has more of potential to be abused than amphetamines.
What are the half-lives of amphetamine, methamphetamine, cocaine, cathinone, and methylphenidate?
Amphetamine - 10 hours Methamphetamine - 11 hours Cocaine - 1 hour Cathinone - don't really know but around 1.5 hours Methylphenidate - 2 hours
What are the monoamines?
A family of neurotransmitters that comprise two subtypes - catechlomines and indeolomines.
Describe the process through which dopamine and then norepinephrine is produced.
IGNORE
Describe the process through which serotonin is produced.
IGNORE
How many dopamine receptors are there and what type of receptors are they?
5 dopamine receptors. They are metabotropic.
Which dopamine receptors are inhibitory and which ones are excitatory?
D1/D5 are excitatory. D2/D3/D4 are inhibitory
Generally speaking, how does dopamine travel throughout the brain?
4 pathways
- Mesolimbic dopamine pathway: originate in VTA (somas) and axons terminate in limbic system structures (or. nucleus accumbens, amygdala, and hippocampus
- Mesocortical dopamine pathway: originate in VTA (somas) and axons terminate in the frontal cortex (specifically prefrontal cortex)
- Nigrostrial dopamine pathway: original in substantial nigra and terminate in basal ganglia (these neurons liked to Parkinson’s)
- Tubero-infundibular dopamine pathway: originates in hypothalamus and terminates in the pituitary gland (secretion of prolactin from the pituitary gland; hormone for maternal behavior)
What is norepinephrine and what is epinephrine?
Both catecholamines. Epinephrine is synthesized further from norepinephrine. Epinephrine shares functions of norepinephrine in the brain but has little unique impact on brain function or psychoactive drug actions of its own.
How many noradrenergic receptors are there and what types of receptors are they?
5 receptors. They are metabotropic.
Which noradrenergic receptors are inhibitory and which ones are excitatory?
alpha1, beta1, beta2 and beta 3 are excitatory.
alpha2 is inhibitory.
How does norepinephrine travel around the brain and act on specific brain regions?
Cell bodies for norepinephrine are mostly found in the locus coeruleus, and axons from these neurons are sent to many areas throughout the brain, including the cortex, amygdala, and structures in the hindbrain.
How many serotonin receptors are there and what types of receptors are they?
7 5-HT receptors. All are metabotropic except 5-HT3 which is ionotropic
Which serotonin receptors are inhibitory and which ones are excitatory?
5-HT1 and 5-HT5 are inhibitory and the rest (2,3,4,6, & 7) are excitatory.
Where are serotonin receptors predominantly found?
Cell bodies are predominantly found in the raphe nuclei, which are found in the brain stem near structures for dopaminergic and noradrenergic neurons, Serotonin pathways terminate in structures throughout the brain.
What is the drug action of amphetamines?
Increase synaptic dopamine levels via 2 mechanisms:
- expels dopamine from the neuron through dopamine membrane transporter. It is able to cause a reversal in the direction of the dopamine transporter (on the axon terminal)
- AT HIGH DOSES, amphetamine prevents dopamine storage. Amphetamine and methamphetamine do this by entering dopamine storage vesicles through the vesicular transporter and displacing dopamine
*both also enhance serotonin and norepinephrine levels through acting at axonal terminals but do so to a lesser extent than dopamine.
What is the drug action of methylphenidate and cathinone?
The action of methylphenidate resembles amphetamine.
1) prevents the reuptake of monoamines (not as effectively as amphetamines)
and
2) prevents the storage of dopamine in synaptic vesicles.
*cathinone’s mechanism of action isn’t as clear but it is thought to rely on the same two mechanisms.
What is the drug action of cocaine?
- primary mechanism involves the prevention of monoamine reuptake by blocking the monoamine membrane transporters.
- cocaine increases the transport of dopamine into synaptic vesicles (more stored dopamine for release)
- increased concentration of dopamine in nucleus accumbens leads to activation of dopamine receptors
a. D2 receptor activation contributes to
rewarding effects of cocaine.
b. D1 receptor activation on GABA neurons
in nucleus accumbens accounts for
associations of stimuli with cocaine’s
rewarding effects. (anticipating drug
produces more activation of these
receptors - in high concentrations, cocaine acts as a Na2+ channel blocker (locally this can act as an anaesthetic + vasconstricter) but this generally results in serious adverse effect/death
What is CART?
A peptide neurotransmitter that is produced after psychostimulant administration. Acute administration causes activation of the gene for CART, leading to the synthesis of CART peptides in axon terminals where they increase dopamine release into synapse.
*predominantly found in the hypothalamus and mesolimbic dopamine system
- increases in locomotor activity
- but if it is produce with psychostimulant drug it counteracts the psychostimulant’s effects.
- REGULATORY EFFECTS.
What are the physiological effects of psychostimulants?
Airway relaxation, Blood vessel constriction, Dry mouth, increased HR, inhibited digestion, increased body temp, pupil dilation, tooth decay with chronic use.
What are the behavioral effects of psychostimulants?
Increased motor activity, psychosis (including hallucinations; formication with cocaine)
- at lower doses it produces an increase in purposeful behaviour
- at higher doses it produces an increase in purposeless behaviour
What are the subjective effects of psychostimulants?
Agitation, Anxiousness, Euphoria, Improved sense of well-being, Increased alertness, Increased energy.
How do sensitization and tolerance occur for psychostimulant use?
- sensitization tends to occur for purposeless behaviour
- repeated administration (may) leads to incentive salience
- tolerance occurs to the positive subjective effects of psychostimulants (always chasing that first high!)
- pharmacodynamic tolerance - especially due to changes in D2 receptor sensitivity
- cross-tolerance occurs between psychostimulant drugs
- sensitization tends to occur after period of intermittent dosing of psychostimulants
- tolerance tends to occur after continuous dosing of psychostimulants.
What happens in addiction to psychostimulants? What happens when there is a dopamine deficit vs. a serotonin deficit?
IGNORE
What are some therapies and treatments for psychostimulant addiction?
- Disulfram inhibits (aldehyde dehydrogenase) and dopamine beta-hydroxylase —> diminishes positive subjective effects and enhances negative subjective effects
- Modafinil elevates dopamine levels in the nucleus accumbens —> substitute for psychostimulant effects to diminish withdrawal; may prevent relapse.
What are psychostimulants?
Drugs that increase psychomotor and sympathetic nervous system activity as well as improve alertness and positive mood.
