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Lecture

PSYC62_Lecture_2.docx

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Department
Psychology
Course
PSYC62H3
Professor
Suzanne Erb
Semester
Winter

Description
PSYC62: Drugs and the Brain Lecture 2: Principles of Pharmacology (Chapter 3) Principles of Pharmacology  Drug-receptor interactions  Dose-response functions  Drug-drug interactions  Pharmacokinetics Drug-Receptor Interactions ( Important basic concepts:)  Receptors: o Large protein molecules that drugs and naturally occurring chemicals of the body act on to exert their effects.  Ligands: 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)  Affinity: 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)  Intrinsic activity: 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 Indirect agonist  A drug that does not interact directly with a receptor but enhances the amount of endogenous ligand available for the receptor.  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 Partial Agonist  A drug that is not as effective as a full agonist but is more effective than an antagonist.  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 baseline  Agonist may increase anxiety and the inverse agonist will decrease the activity Competitive antagonist  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 Non-competitive 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 Dose-response Functions  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
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