Lecture 16: Drugs and Synapses Flashcards
What are the 3 main ways of classifying psychoactive drugs?
- pharmacology
- physiology
- sociology
What are psychoactive drugs?
drugs that act on the brain – almost exclusively, at chemical synapses
Psychoactive Drugs Classified by Target
What are the 3 targets?
psychoactive drugs can be classified by their targets (in neurotransmitter signalling cycle) and the actions they exert upon them
- transporters (or any process where a first messenger is recycled by nearby cells)
- enzymes (targeting transmitter synthesis or transmitter breakdown)
- receptors (for neurotransmitters or other signalling molecules – ie. hormones)
Psychoactive Drugs Classified by Target
What kind of transporters (or any process where a first messenger is recycled by nearby cells) can be targets? (2)
- inhibitors (antagonists)
- reversers
Psychoactive Drugs Classified by Target
What kind of enzymes (targeting transmitter synthesis or transmitter breakdown) can be targets? (2)
- inhibitors
- precursor supplements
Psychoactive Drugs Classified by Target
What kind of receptors (for neurotransmitters or other signalling molecules – ie. hormones) can be targets? (3)
- agonists
- antagonists
- inverse agonists
What are inverse agonists?
antagonist drug that acts on a metabotropic receptor to reduce the activity of its signalling transduction cascade to a level BELOW basal (resting) activity of that pathway in an unstimulated cell
What must psychoactive drugs do?
get into CNS, bind target molecules, and resist degradation
Within a particular class (types of drug action), how can we classify various properties of a specific individual drug?
What are the properties?
by how it affects the nervous system (pharmacodynamics vs. pharmacokinetics)
- solubility
- selectivity
- affinity
- longevity (half-life)
What is pharmacodynamics?
how a drug affects the body
What us pharmacokinetics?
how the body affects a drug
What is solubility?
Does it affect pharmacokinetics or pharmacodynamics?
ability to enter the bloodstream, and ability to cross the BBB
pharmacokinetics (how the body affects a drug): affects ‘bioavailability,’ mode of effective administration, and whether CNS effects will occur
What is selectivity?
Does it affect pharmacokinetics or pharmacodynamics?
ability of the drug to also bind and affect other proteins
pharmacodynamics (how a drug affects the body): affects the number of ‘off-target’ side effects that could be experienced
What is affinity?
Does it affect pharmacokinetics or pharmacodynamics?
ability of the drug to bind its target site and activate/inactivate receptors
pharmacodynamics (how a drug affects the body): affects the concentration of a drug needed to see an effect
What is longevity (half-life)?
Does it affect pharmacokinetics or pharmacodynamics?
ability to resist degradation by enzymes, or excretion by liver and kidneys
pharmacokinetics (how the body affects a drug): affects ‘bioavailability,’ and how long the effects of the drug will persist for
What can affinity be measured in terms of? (2)
- one drug acting on different receptors
- different ligands acting on one receptor (more common)
What is affinity reported in terms of?
Kd – the concentration of the drug which will bind half the available receptors
What factors cause drug-receptor interactions to be complex and diverse, and act on multiple systems?
- lack of selectivity
- ubiquity (nervous system)
- ubiquity (non-nervous)
Why might a drug be multi-functional due to lack of selectivity?
it shows promiscuity – can bind to and activate/inactivate more than one type of receptor/transporter/enzyme
Why might a drug be multi-functional due to ubiquity (nervous system)?
the same receptor/transporter enzyme is present on different neurons in distinct brain circuits with distinct functions
Why might a drug be multi-functional due to ubiquity (non-nervous)?
it also targets receptors that lie outside the nervous system (ie. drugs targeting adrenergic receptors – L17)
What are amphetamines?
good examples of drugs that bind to multiple targets (lack of selectivity)
- can interact with multiple different proteins in aminergic neurons – including transporters, degrading enzymes, and vesicular transporters
- BUT they have different relative affinity (binding strength), and therefore different potency with different targets
Which biogenic amine’s (NE, DA, 5-HT) levels will be most affected by amphetamine?
NE – amphetamine will work most effectively at low concentrations of norepinephrine
(a decent amount of amphetamine will have a noticeable effect on dopamine (DA) too)
What are some psychoactive drugs that cause relaxation?
What is the mechanism?
drugs: alcohol, downers (ie. barbiturates), ketamine, Xanax/Ambien
mechanism: enhance GABA signalling
What are some psychoactive drugs that cause reward?
What is the mechanism?
drugs: cocaine, amphetamines, opiates/opioids
mechanism: enhance dopamine and/or norepinephrine signalling
What are some psychoactive drugs that cause euphoria/mood elevation?
What is the mechanism?
drugs: MDMA (ecstasy/molly), amphetamine, SSRIs, SNRIs
mechanism: enhance serotonin and or NE signalling
What are some psychoactive drugs that cause pain relief?
What is the mechanism?
drugs: opiates/opioids, cannabis, gabapentin
mechanism: variable mechanisms
What are some psychoactive drugs that cause concentration/alertness?
What is the mechanism?
drugs: caffeine, tobacco/nicotine, uppers (ie. amphetamines, ritalin/adderall)
mechanism: enhance cholinergic or biogenic amine signalling
What are some psychoactive drugs that cause unusual perceptual experiences?
What is the mechanism?
drugs: LSD, MDMA, cannabis, psilocybin, mezcal, ketamine
mechanism: variable mechanisms (though a number are 5-HT subtype selective agonists)
What do many recreational drugs (drugs of abuse) target?
CNS neuromodulator neurotransmitter systems
What are the similarities in the way aminergic systems (biogenic amines) are organized?
- project widely throughout the brain
- signal principally through metabotropic receptors
- often have modulatory effects
- each system has a different pattern of targets and receptor subtypes
- there is crosstalk between these networks
*within your brain there are also systems of (cholinergic) ACh-releasing neurons based in the brainstem and basal forebrain that are organized in very similar ways – their synapses are the targets of nicotine
What are the three different organizing questions to discuss psychoactive drugs?
How real is the line between medical and recreational psychoactive drugs?
Where and why do we draw distinctions between tolerance, dependence and addiction?
How and when do overdoses occur?
Medical vs. Recreational Drug Use Case Study: Dopaminergic Signalling in Disease
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What is Parkinson’s disease?
progressive neurological disease characterized by movement-related symptoms (rigidity, tremors), depression, and subtle cognitive deficits
What is Parkinson’s disease caused by? What is the primary treatment?
loss of DA neurons from substantia nigra (in midbrain)
primary treatment is L-DOPA, which increases amount of DA available to be released
What are the side effects of Parkinson’s disease?
more than 50% of people who take L-DOPA experience episodes of drug-induced psychosis
What is schizophrenia?
neurodevelopmental disorder characterized by hallucinations, withdrawal, catatonia, cognitive disruptions, and distortions
What is schizophrenia caused by? What is the treatment?
unclear (probably multiple causes)
however, some symptoms can be treated by antagonists to D2Rs (ie. haloperidol, chlorpromazine)