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University of Toronto Scarborough
Suzanne Erb

Drugs & The Brain - Lecture 1 Friday, January 14th, 2011 Basic Principles of Pharmacology 1. Defining pharmacology and psychopharmacology 2. Defining drugs 3. Drug-receptor interactions 1. Defining pharmacology and psychopharmacology Pharmacology: Discipline that examines the effects that drugs have on biological systems (including nervous and non-nervous tissues) Psychopharmacology: Discipline that examines the effects that drugs have on behavior and mental processes, including cognitions and emotions; sub- discipline of pharmacology that focuses on the drug interactions on the CNS; includes study of recreational drugs (high-abuse potential) and ones used for modification of behaviour and alleviation of symptoms (ie. depression, schizophrenia, addiction, etc.) Pharmacy: pharmacology an important part of training, but it is a sub- discipline Psychoactive drugs do interact with non-nervous tissue, and these effects are extremely important to understand, even though psychopharmacology generally focuses on the effects of the CNS. What distinguishes a course in psychopharmacology from one in pharmacology? - a great deal of overlap between these two because the basic principles do apply to both - psychopharmacology has the greater focus on the CNS - pharmacology usually studied in medicine, however psychopharmacology may be administered in a psychology department 2. Defining drug Defining drug is a lot easier said than done. It is very difficult to define with one single comprehensive definition because there are different meanings depending on the context (colloquially, by the government, law, etc.). Merriam-Webster defines it in four ways. They are good, accurate and appropriate, but they describe only one sub-group. They are describing drugs primarily used for medicinal purposes, not recreational in one definition and vice versa in another. #4 gets closer to defining it in a global way, but its not perfect. It is too general, there are other substances we ingest on a regular basis that have this same function. Even for Grilly, its not specific enough. A chemical could be a neurotransmitter, an endogenous substance. Although these substances have been isolated to be used as medications (ie. adrenaline for anaphylactic shock, insulin for diabetes, L-dopa for Parkinsons disease, etc.). Psychoactive drugs sometimes referred to as psychotropic drugs, they are used interchangeable. They both interact with nervous tissue to affect cognition, emotion and behaviour. 3. Drug-receptor interaction Ligands: biologically active chemicals in the body (ie. hormones, neurotransmitters, neurohormones, etc.) Affinity: key-lock theory; the molecular structure of the drug capable of binding to the molecular structure of the receptor; several different drugs may all be able to bind, some having higher affinities than others Intrinsic activity: the relative capability of a compound to activate a receptor after binding with it; how able is the key to fit the lock, to turn the lock, and open the door (some may have affinity for the lock with nothing in terms of turning the lock, some might have more difficulty turning the lock) NB: there is no direct correlation between these concepts of affinity and intrinsic activity Different kinds of drug-receptor interactions... 2 types of interactions on a general level that drugs can have with their receptors, the nature of interaction is defined by the affinity and level on intrinsic activity. Agonist: compound that activate a receptor (have some degree of affinity and intrinsic activity and that receptor) Antagonist: compound that blocks the actions of agonists (ones that block the actions of agonists, they have a degree of affinity, but no intrinsic activity occurs) Indirect agonist: a drug that does not interact directly with a receptor but enhances the amount of endogenous ligand available for the receptor (cocaine does this, it binds to the transporters in the pre-synaptic neurons, blocking dopamine to be taken up, increasing the concentration of it and its availability, this is the primary means by which cocaine affects the CNS (it does it through other monoamine interactions as well)) Partial agonist: a drug that is not as effective as a full agonist but is more effective than an antagonist (competes for the receptors with the full agonist, which affects the complete effect the full agonist can have on the body, creating an antagonist-like effect, because it reduces the ability of the full agonist) Inverse agonist: a drug that acts at the same receptor as an agonist but that produces effects opposite those of the agonist (competition at the binding sites again, the inverse agonist will counter the effects of the agonist, ie. inverse agonist of benzodiazepines: a series of drugs that induce anxiety and see the effects that it has, perhaps understanding it better and finding other methods of helping anxiety) Competitive antagonist: an antagonist that is capable of dissociating from the receptor, allowing for competition between the agonist and antagonist for the receptor (eventually the antagonist will dissociate, giving an opportunity for the agonist to bind) Non-competitive antagonist: an antagonist that is not capable from the receptor (this will have a greater effect than the competitive antagonist) Mixed agonist-antagonist: a drug that acts as an agonist itself but blocks the activity of another agonist in the same system (majority act as partial agonists, but can also act as an antagonist, blocking another drug that would be able to gain access)(prevents another drug that has affinity to bind to the receptor to bind and have effects)(many opioid drugs, and the treatment of opiate addiction, treatment of anxiety have this type of mixed interaction) Drugs & The Brain - Lecture 2 Friday, January 21st, 2011 Principles of Pharmacology and Pharmacokinetics Drug-receptor interactions: the relationship between ligands such as dopamine with their receptors. Drugs can essentially act like ligands to mimic the effects of ligands or they can act to alter the effects of those chemicals. Two important concepts for understanding the nature of interaction: affinity and intrinsic activity. Affinity: to what degree does the drug fit the receptor? What is the question? Can you use the key thats fit into the lock to open the door and do you have to struggle to get it open? What is the relationship between affinity and intrinsic activity? No direct relationship between the degree of affinity or the amount of intrinsic activity (ie. you can have a high affinity but a low IA, or high levels of both). They are related in that you can have one without the other. (Note: antagonist) Two general kinds of drug receptors: agonist or antagonist Agonist: drug binds to the receptor, can activate it, some intrinsic activity. Antagonist: drug binds, blocks the action of agonists, no intrinsic activity. Mixed agonist-antagonist: a drug that acts as an agonist itself but blocks the activity of another agonist in the same system; can act as an agonist or an antagonist; its acting act some receptor subtypes (ie opioid receptors) (maybe a partial agonist) and acting as an antagonist at another population of receptors (where it will antagonize the effect the drug has on particular receptors). What are dose-response functions? (Be comfortable with this and understanding what kind of information theyre presenting.) How the amount or concentration of a drug in a system at a synapse affects a physiological response. Does it have more of an effect at higher doses, lower doses? Dose-response functions express how that relationship looks. It can be defined as a graphical representation to expression of a dose...
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