How Drugs Affect our Behavior Flashcards
Receptor agonist vs agonist
- agonist is endogenous, receptor agonist is exogenous
Competitive vs noncompetitive antagonists
- Competitive antaagonist: blocks agonists from binding to the receptors
- Noncompetitve antaagonist: bind to target receptors at a site that is different from where the endogenous ligand binds
What does it mean to have a low affinity for a receptor?
- If a particular drug has a low affinity for a receptor, then it will quickly uncouple from the receptor
- To bind half the receptors at any given time, a higher concentration of the drug is needed
What does it mean if a drug has a high affinity?
- the receptor and the drug will stay together for a longer time, and a lower concentration of drug will be sufficient to bind half the receptors
What happens when there are equal concentrations of a low affinity and a high affinity drug?
- the high affinity drug will be bound to more receptors at any given time
- if the drugs have an equivalent effect on the receptors, then the higher affinity drug will be more potent
What is an effective dose?
- The basic dose-response curve plots increasing drug doses against increasing strength of the response being studied.
- An effective dose is the dose at which the drug shows half of its maximal effect
What is potency?
- Relative potencies are assessed by comparing the ED50 values
- In the example, both drugs have comparable effects, but one of the drugs has the effects at lower doses, and therefore is more potent
What is efficacy?
- Drug efficacies are compared by evaluating maximal responses, rather than doses
- drug with greater maximal effect has higher efficacy
What is a partial agonist/antagonist?
A drug of only moderate efficacy
Phencyclidine
- PCP or Angel Dust
- NMDA receptor antagonist
- Mind altering drug that may lead to hallucinations
- Ketamine has similar effects
NMDA Antagonists symptoms
- Loss of responsiveness (not consciousness)
- Loss of sense of self/identity
- Dissociation
- Psychotic thoughts
- Sensory aberrations
- Aggression and agitation (rare)
NMDA and Schizophrenia
- Because NMDA receptor antagonists, such as PCP, are psychotomimetic (elicit psychotic symptoms in people), it may be reasonable to assume that NMDA receptors are naturally sub-functional in people with psychotic disorders
- If that is true, may drugs that enhance NMDA receptor function be of benefit to them?
GABA-A Receptor
- Cl- channel
- Has multiple binding sites for other substances
- These are inbolved in allosteric (enzyme) regulation/modulation
Positive allosteric modulators examples
- Valium
- Lunesta
- Clonazepam
- Ambiem
Ethanol
- beverage alcohol
- Calming, anxiolytic, and sedative/hypnotic effects of alcohol depend upon GABA-A receptor positive modulation
What is the dark side of positive modulators?
- drugs violate homeostasis
- receptor desensitization (down-regulation): fewer functional receptors=less drug-induced imhibition, doesn’t always involve fewer receptors
- tolerance
Norepinephrine/Dopamine and ADHD
- All medications for ADHD influence the norepinephrine and dopamine systems
- Some block NE and/or DA reuptake via the transporter (Ritalin, Focalin, Strattera)
- Some cause NE and/or DA release (Adderall, dexedrine, vyvanse)
Serotonine reuptake inhibitors
- Enable serotonin to stay in the synapse for longer
- Prozac, paxil, celexa, zoloft, luvox
What are opioids?
- Ex. morphine, heroin, oxycodone, fentanyl
- Analgesic and addictive properties
What are the three opioid receptors?
- delta
- kappa
- mu
- All opioids have a high affinity for mu receptors but will also bind to the others
What are the three endogenous opioids?
enkephalins, endorphins, and dynorphins
What are naloxone and naltrexone?
opioid antagonists used to treat alcohol use disorder
How do opioids increase dopamine release?
- indirectly
- opiods bind to mu opioid receptor on GABA neuron
- when GABA is released on the GABA-A receptors on the dopamine neuron, the dopamine neuron will not fire
- When opiod is binding to GABA (blocking), GABA is not released. So, dopamine can be released easier (with no inhibition)
What type of drug is nicotine?
A stimulant
What receptor does nicotine bind to?
nicotinic acetylcholine receptors (nACh), calcium and sodium ion channel
What does nicotine increase the release of?
- increases dopamine release
- when nicotine binds, acetylcholine is also released, leading to increased dopamine release
may also affect other neurotransmitters like norepinephrine
What does a positive allosteric modulator do?
- the allosteric modification may result in enhancement in the binding affinity of the ligand with the orthosteric site causing boosting of a signal or increased activity
What type of drug is cocaine and what does it do?
- stimulant
- blocks the dopamine transporter to increase the amount of dopamine available in the postsynaptic cleft (prevents dopamine reuptake, also norepinephrine and serotonin)
- allows for longer activation of the postsynaptic cell
How do amphetamines work/what do they do?
- Enters presynaptic terminal via DA transporter
- Packaged into vesicles in place of dopamine
- Excess dopamine pumped out of cell via DA transporter
- Increased dopamine release into synaptic cleft (also norepinephrine and 5-HT)
reverses function of transporters allowing them to push out dopamine instead of bringing it inwards
What type of drug is alcohol?
initial stimulant, prolonged depressant, sedative (unique in this range of effects)
What receptors does alcohol act on and what does it do?
- Enhances GABA-A receptor activity
- reduces NMDA (glutamate receptor) activity
Low dose alc vs High dose
- Low dose alcohol stimulates dopamine release- neurons are allowed to fire due to disinhibition
- At high doses, more ubiquitous action that suppresses the overall system leading to sedative effects
