PSYC62H3 Lecture 3: Pharmacokinetics and Pharmacodynamics
PSYC62
LECTURE 3
Receptor Action: Behaviour
• Types of action:
o Agonist vs Antagonist
▪ agonist → has same effect that the endogenous ligand has at the receptor
• Mimics a ligand
• Doesn’t necessarily mean ‘positive’
▪ antagonist → blocks effect of endogenous effects
o Competitive (e.g. haloperidol - DOPA, antagonist) vs noncompetitive (e.g. ketamine -
NMDA, antagonist)
▪ Competitive → compete for same spot the endogenous ligand binds to
▪ Noncompetitive → bind to diff site on receptor and cause some impact
• Ex: ketamine
• Noncompetitive antagonist (blocks or inhibits the effect glutamate
ligand would usually have)
• Receptor sites:
o Active site vs. allosteric site
▪ Active site: where endogenous ligand usually binds
▪ Allosteric site: sites that are not the normal site on the receptor
• Modulator action:
o Positive vs negative modulation
o Don’t necessarily have an agonistic or antagonistic effect
• Channel is ionotropic
o Associated with receptor
• Modulation increases or decreases the likelihood a ligand will have it's full effect when it binds
to its receptor
• Positive and negative modulation DIFFERENT from agonist and antagonist action
o Agonists and antagonists start or stop
o Modulators change efficiency
▪ Ex: increase/decrease voltage to open, length of time a receptor is open
• Partial agonist
o Different from positive modulation
PSYC62
LECTURE 3
o will bind to receptor and cause effect as the endogenous ligand but not to the FULL
extent
Receptor Action : Metabotropic vs. Ionotropic
• Ionotropic
o Immediate and fast acting - transiency
o Almost all ionotropic receptors are going to have different subunits
• GABA receptor opens and allows Cl- to enter the cell
o Hyperpolarizing effect on postsynaptic neuron (away from sending an AP)
• Metabotropic
o Delayed but long lasting - permanency
o “Enhancement” of overall system
o If a receptor is metabotropic means it doesn’t have an ion channel apart of it
o Have impact by influencing intracellular chemical reactions
• Activated adenylyl cyclase can have a number of effects
o Lead to change in expression of different proteins in neuron by affecting the
constituents of the nucleus
PSYC62
LECTURE 3
• 4 diff types of receptor-mediated drug action
• Agonist
o Drug docks with receptor and when it binds it activates a g-protein cascade which can
take more than one route
o Impact mimics endogenous ligand
• Antagonist
o Drug binds to receptor but g-protein on inside isn't activated
o Normal process doesn’t occur
• Partial agonist
o G protein activated
o May or may not facilitate the cascade or to the full effect
• Inverse agonist
o Drug is recalling a previously activated g protein complex and it turns it off
o Stops what has already started
o Can have an agonist that’s already bound and inverse agonist comes and turns it off
▪ Inverse effect on what was previously agonistic
Neurotransmitters
• Synthesized in various places of the cell
o Soma
▪ Transportation needed to terminal
o Presynaptic terminal
▪ Able to replenish more quickly than those generated in soma
• Diverse set of biochemical pathways
o Drugs target either transmitter itself, precursors, or enzymes involved in synthesis or
catabolism
o Drugs can also modulate transport proteins and various other mechanisms
• It’s the AXONS themselves that project
o To the destinations
Document Summary
Lecture 3: will bind to receptor and cause effect as the endogenous ligand but not to the full extent. Lecture 3: 4 diff types of receptor-mediated drug action, agonist, drug docks with receptor and when it binds it activates a g-protein cascade which can take more than one route. Impact mimics endogenous ligand: antagonist, drug binds to receptor but g-protein on inside isn"t activated, normal process doesn"t occur, partial agonist, g protein activated, may or may not facilitate the cascade or to the full effect. Inverse agonist: drug is recalling a previously activated g protein complex and it turns it off, stops what has already started, can have an agonist that"s already bound and inverse agonist comes and turns it off. It"s the axons themselves that project: to the destinations. Serotonin: an indoleamine, mood, appetite, and sleep, transport, vesicular monoamine transporter 2 (vmat2) Neurotransmitters: norepinephrine and epinephrine: norepinephrine, catecholamine, further synthesized into epinephrine, associated with needful action, ex: sympathetic.
