1. Psychopharmacology (psychoactive drugs)
Name ways to get a drug into your system (sources of drug administration)
Rank those sources based on how fast they reach blood & thus the brain
List the factors that determine the effect of a drug on an individual. (In other words, what makes a psychoactive drug be more effective in one person than another)
Psychopharmacology: Examines the relationship between drugs and psychological processes
The study of drugs that affect mood, thought or behavior
What’s a drug?
Salt, vitamins, milk? Well, you say, these are normally found in out bodies (they are endogenous), so a drug is a foreign substance (exogenous).
What about L-Dopa?, which is an endogenous brain substance which is turned by the brain into dopamine, a neurotransmitter. L-Dopa is given to Parkinson’s disease patients to treat their symptoms… drug or not?
There is evidence that we may have morphine normally present in our bodies (not endorphins, but actual morphine)-- if true, then morphine isn’t a drug anymore?
how about olestra, which is a fat substitute that IS fat, but is too big to be digested so goes right through our body (although as far as the taste buds are concerned, it was fat)…drug or not?
OK, so maybe a drug is a substance that changes the “normal” body chemistry
but so does learning, emotions
So, much like any other concept, there is no ‘golden rule’ to discriminate whether something is a drug or not, but there are many properties that a ‘prototypical’ drug has, such as (1) being exogenous, (2) change normal chemistry, etc.
Group activity

2. Outline Pharmacokinetics Pharmacodynamics
Dose-response curve
Pharmacodynamics
Drugs vs. NTs
Agonists vs. Antagonists
Receptor types
Tolerance
Specific Neurotransmitter Systems (& drugs that affect them)

3. Pharmacodynamics Pharmacokinetics Whatever the body does to the drug
how drugs are
absorbed,
distributed within the body,
metabolized, and
excreted.
Whatever the drug does to the body
Main effect: increasing or decreasing the effect of neurotransmitter X
Side effects (unwanted effects)
All drugs have side effects this is because the CNS uses the same chemicals (neurotransmitters) in overlapping circuits (brain structures) to produce complex changes in behavior in other words, no chemical mediates a single behavior
Pharmacokinetics: The process by which drugs are absorbed, distributed within the body, metabolized, and excreted.

4. Pharmacokinetics Sources of administration:
oral, intranasal, inhalation, topic, intravenous (i.v), sublingual, intramuscular (i.m.) subcutaneous,
intraperitoneal
Distribution:
Lipids (fats) vs. non-lipids (proteins, ionized molecules)
Metabolization: liver
Excretion: kidneys
Half-life: time it takes to eliminate half the drug from the bloodstream. It is used to determine inter-dose interval
Intravenous (IV) injection: Injection of a substance directly into a vein.
Intraperitoneal (IP) injection: The Injection of a substance into the peritoneal cavity-the space that surrounds the stomach, intestines, liver, and other abdominal organs.
Depot Binding: Binding of a drug with various tissues of the body or with proteins in the blood.
Albumin: A protein found in the blood, serves to transport free fatty acids and can bind with some lipid soluble drugs Plasma half-life .

5. Ways to administer a drug (& time to reach blood)

7. therefore, how much “door opening” you get is a function of:
number of keys (ligand concentration)
number of locks (protein concentration)
fit (affinity)
ability to open lock (intrinsic activity)
all other things being equal, the higher the dose of drug you give, the higher the ligand concentration is going to be at the relevant binding sites, the more proteins are going to be activated, and the bigger biological effect you’re going to have
you can present the relationship between dose and biological effect (or response) graphically; a dose-effect or dose-response curve (or function)
to make one, you simply give subjects a range of doses, and measure and plot their responses (make a D-R curve on the blackboard)
dose is virtually always presented in mg/kg of drug, on the x-axis (sometimes a log scale will be used)
response is presented in whatever objective or subjective scale is relevant, and on the y-axis; usually, up means a bigger effect
Dose-response curve: Effect of a drug as a function of the amount of the drug administered.

8. Therapeutic index: The ratio between the dose that produces the desired effect in 50% of the animals and the dose that produces toxic effects in 50% of the animals.

9. Pharmacodynamics A drug can do only two things, either:
Increase the effect of neurotransmitter X (agonist)
Decrease the effect of neurotransmitter X (antagonist)
Thus, in order to understand the action of a ‘drug X’, we need to understand the neurochemical system it interacts with.
In other words, we need to understand how Neurotransmitter X
- is produced & released from the pre-synaptic neuron
acts on the receptors of the post-synaptic neuron
is removed from the synaptic cleft

10. Pre-synaptic receptors Post-synaptic receptors 2. pack 3. release
- -
precursors
2. pack
3. release
NT ‘x’
4. Bind
1. produce
5. Post-synaptic
changes
(e.g., epsp)
+ +
AP  Ca++ inflow
6.A Recycle
6.B Destroy
Each of these steps has a technical term and is a potential mechanism of action for drugs
Produce = Synthesis
Recycle = reuptake
Destroy = enzimatic degradation
Metabolite (the ‘destroyed’ substance)
Drugs can also act by mimicking neurotransmitter by binding and activating (or not):
Presynaptic receptors
Postsynaptic receptors
Pre-synaptic
Neuron
(axon)
synaptic
cleft
Post-synaptic
neuron
(dendrite)

12. Copyright © Allyn & Bacon 2004

13. Metabotropic Receptors
Receptors are specific for individual neurotransmitters
More than one receptor for each neurotransmitter e.g., Acetylcholine (muscarinic & nicotinic receptors)
Ionotropic Receptors
(e.g., nicotinic)
Metabotropic Receptors
(e.g., muscarinic)
Metabotropic Receptors:
- Open Ion Channels
- Alter intracellular environment
- Affect gene transcription: affect structure/function of cell
a ligand (any relatively small molecule) diffuses around, and binds to a receptor, ( usually a protein )
ligands can be hormones, neurotransmitters, or drugs;
> 300 receptors, probably more like a thousand; 16 for serotonin
proteins embedded in the cell membrane, are perfect for getting information (like the presence of drugs) from the outside of a cell to the inside!

14. Agonists and Antagonists
Agonist (Greek: Agon, meaning contest)
Substance that facilitates post-synaptic effects
Antagonist
Substance that inhibits or blocks the post-synaptic effects

15. Exogenous vs. Endogenous (drugs vs. neurotransmitters)
Partial Agonist- binds to a receptor, and has less intrinsic activity than the endogenous ligand
Inverse Agonist- binds to a receptor and produces an effect that is opposite to that of the endogenous ligand
Agonist – mimics the natural (endogenous) ligand (Neurotransmitter)
Direct agonist – binds to post-synaptic receptor and exerts same effects
Indirect agonist – block re-uptake, inhibit degrading enzyme, increase release.
Antagonist
Blocks the post-synaptic receptor, in a direct (binds to receptor but doesn’t activate it) or indirect fashion (increased enzymatic degradation, decreased release via autoreceptor stimulation)
Noncompetitive binding:
Binding of a drug to a site on a receptor; does not interfere with the binding site for the principal ligand.
Indirect antagonist:
A drug that attaches to a binding site on a receptor and interferes with the action of the receptor; does not interfere with the binding of the principal ligand.
Indirect agonist:
A drug that attaches to a binding site on a receptor and facilitates the action of the receptor; does not interfere with the binding site of the principal ligand.
Affinity – how well the drug or neurotransmitter binds to the receptor – how long it stays bound.
Efficacy – the effect of the drug (stimulate the receptor or block the receptor).
Exogenous vs. Endogenous (drugs vs. neurotransmitters)
Agonist vs. Antagonist: Both bind to a receptor. The agonist activates it, the antagonist does not (antagonists block the receptor)
Competitive vs. non-competitive: whether the drug works at the same receptor as the NT or at a different receptor as the NT, but one that modifies the NT’s action

16. Will an antagonist produce a rightward shift or a leftward shift in the dose-response curve? (graph)
How would a competitive antagonist modify the curve? (draw with a solid line)
How would a non-competitive antagonist modify the curve (draw with a dotted line)
Group activity

17. Tolerance a decreased response due to frequent use.
Metabolic tolerance: faster metabolism of the drug.This is a pharmacokinetic mechanism (e.g., alcohol metabolization by hepatic enzimes)
Cellular-adaptive tolerance: down-regulation of receptors (a pharmacodynamic mechanism)
Example of metabolic tolerance: alcohol and hepatic function
Before drug
After Drug

18. Factors that determine the effect of a drug on an individual
Age
Weight
Setting in which the drug is used
History of use (tolerance)
Level of proteins in blood
Time of day drug is consumed
These effects are underlined by both pharmacokinetic and pharmacodynamic modulations
set: what the user brings to the drug
6 pack after a promotion
after getting fired
expectations
setting: social and physical environment in which the drug is taken
culture (Irish vs. Japanese)