PSYC62: Drugs and the Brain
Lecture 2: Principles of Pharmacology (Chapter 3)
Principles of Pharmacology
Drug-Receptor Interactions ( Important basic concepts:)
o Large protein molecules that drugs and naturally occurring chemicals of the body act on to exert their effects.
o Biologically active chemicals in the body (e.g., hormones, neurotransmitters, neurohormones, etc)
o Can also extended to include drugs - which also react at receptors - bind of the ligand to the receptor in a highly
specific way and will mostly only bind to its selective type - once the ligands binds , it changes in membrane
potential, after its done its job its either metabolized or reuptake - drugs will act at multiple receptors or could
potentially but will have a tendency to activate at a certain receptor (one that it prefers)
o The ability of a compound to bind to or maintain contact with a receptor.
o The question is simply does the drug bind to the receptor at all?
o The chemical formula determines most of the time as to whether the drug will bind to a certain receptor - key
lock example (a key that goes in easily has high affinity for example)
o The relative capability of a compound to activate a receptor after binding with it.
o Once the ligand has bound to the receptor, does it have a effect at that receptor? Given that the key fits the lock,
does it turn the door handle? (intrinsic activity)
o A drug could have affinity for a receptor but no intrinsic activity for it
o You can have affinity without intrinsic activity but it cannot have intrinsic activity without any affinity Drugs act at receptors as either agonists or antagonists
Agonist - some level of affinity and some level of intrinsic activity
Antagonist - has affinity for the receptor but has no intrinsic activity for the receptor
A drug that does not interact directly with a receptor but
enhances the amount of endogenous ligand available for
Indirect agonist - cocaine is a good example - to increase
the concentration of dopamine in the synape so the
dopamine has a greater potential to change the biologial
activity - increasing the amount of endogenous chemical
and in this case dopamine
Monoamine Reuptake Inhibitor - affects the reuptake of
the dopamine - when dopamine normally has its effects,
it's usually taken up - cocaine binds to the transporter
molecules and blocks reuptake - hence the concentration
of the dopamine increases and thus more effects
A drug that is not as effective as a full agonist but is more effective than
Has less intrinsic activity at the full agonist but it has intrinsic activity
Overall - in the partial agonist will reduce the effects of the full agonist if
the full agonist also binds at the receptors
Overall - it's having a antagonist effect Inverse Agonist
A drug that acts at the same receptor as an agonist but that decreases
basal activity at the receptor and, thereby, produces effects opposite
those of the agonist
Activity at any receptor will associate with a baseline (basal activity) - if
you deliver a agonist, you will increase the activity compared to the
Agonist may increase anxiety and the inverse agonist will decrease the
An antagonist that is capable of dissociating from the receptor, allowing for
‘competition’ between the agonist and antagonist for the receptor.
More common kind of antagonist - given full agonist the agonist effects
should be overcome the antagonist
An antagonist that is not capable of dissociating from the receptor.
They do not dissociate and their bind is permanent -
Will have a bigger effect on the system - Mixed agonist-antagonist
A drug that acts as an agonist itself but blocks the activity of another agonist in the same system.
Buprenoprphine - binds to the receptor and blocks the effects (antagonist) at the new opiate receptor
The relationship between the dose of a drug administered in particular group of individuals and the degree of response or
number of individuals exhibiting the response
Dose-response functions are typically obtained by administering one group a placebo or vehicle, and two or more groups
different doses of the drug of interest.
Dose-response functions are dose, response, and species/age/gender dependent.
Depend on the amount of concentration of the drug, how does that concentration or amount affect that behavioural
response - do higher or lower doses have different effects?
Two ways of dependent variables
o With humans - 0 dose is usually a placebo
o With animals - vehicle is used as 0 dose
The most important factor are the concentration, and the rate of accumulation at the site of activation - these are in turn
affected by other factors and most notably dose
Dose - is expressed g/kg or mg/kg - the greater the body weight, the more drug will be needed assuming all other factors
are kept the same
Response - a couple slides down
Age - young and elderly are stronger and effects are prolonged
Gender - female and male differences in weight, hormones, etc. Response - why the sigmoidal shape instead of 100% linear?
o Any drug has a minimal threshold - requires a minimal amount of receptors has to be reached - there's going to
be a point where no matter