Term
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Definition
| Study of the effects of chemicals on cells & organisms |
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Term
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Definition
| Study of the factors affecting the concentration on the drug at the active site as a function of time (what the body does to the drug) |
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Term
def
Pharmacokinetic process |
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Definition
| ADME - Absorption, Distribution, Metabolism, Excretion |
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Term
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Definition
| The study of how the target cells respond to the delivered concentration of drug (what the drug does to the body) |
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Term
| What are the spectrum of Drug Sizes? (molecular wt) |
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Definition
| Varies from small ions to large proteins |
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Term
| When do drugs have a greater ability to cross biological membranes? |
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Definition
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Term
| How do drugs achieve specificity for target action? |
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Definition
| By targeting receptors that are only expressed on desired cells. |
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Term
| What factors control the concentration of drug at a site at any given time? |
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Definition
| Pharmacokinetic process - ADME. |
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Term
| What are the majority of drug receptors? |
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Definition
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Term
| What are commonly used ligands for receptors? |
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Definition
| Neurotransmitters or hormones. |
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Term
| What happens once a ligand binds its receptor? |
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Definition
| Transduction of the binding to a signal altering the intracellular biochemistry or ionic concentrations to change cellular metabolism. |
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Term
| What are the 4 major receptor classes? |
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Definition
Ligand-gated ion channel
Tyrosine Kinase-linked receptors
G-protein Coupled Receptors
Ligand-activated Transcrption Factors |
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Term
Function:
Ligand-gated Ion Channel |
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Definition
| Change in membrane potential or ionic concentration => cellular effect |
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Term
Function:
Tyrosine Kinase-linked receptors |
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Definition
| Protein phosphorylation => cellular effect |
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Term
Function:
G-protein Coupled Receptors |
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Definition
Intracellular secondary messanger => cellular effect
or
Intracellular secondary messanger => protein phosphorylation => cellular effect. |
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Term
| Function: Ligand-activated Transcription Factors |
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Definition
| Nucleus activation => mRNA => protein => cellular effect |
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Term
| Which receptor type is used by >50% of the currents drugs used? |
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Definition
| G Protein-Coupled Receptors |
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Term
| Besides receptors, what else can be used as drug sites of action? (drug targets) |
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Definition
| other cell components s.a. phospholipids, DNA, enzymes, etc. |
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Term
| Which receptor site works fastest? |
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Definition
| Ligand-gated ion channel : milliseconds |
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Term
| Which receptor site works slowest? |
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Definition
| Ligand-activated Transcrption Factors: hours |
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Term
| How fast do Tyrosine Kinase-linked receptors & G-protein Coupled Receptors work? |
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Definition
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Term
| What are the only 2 post-synaptic drug action site? |
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Definition
| Post-synaptic adrenoreceptors => trigger biological responses Non-adrenergic post-synaptic autoreceptors => modulate actions of post-synaptic adrenergic receptors |
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Term
| What 2 presynaptic receptors do drugs work on? |
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Definition
Pre-synaptic autoreceptors => limit further NE secretion when there's an abundance in the synaptic cleft
Non-adrenergic presynaptic receptors => modulate actions of the pre-synaptic adrenergic receptors |
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Term
| What 3 OMPs are used as drug target sites? |
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Definition
Pre-synaptic NE transporter
The calcium channel
SNAP proteins involved in vesicular exocytosis |
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Term
| What drug action site is a target for cocaine? |
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Definition
| Presynaptic NE transporter |
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Term
| What drug action site is a target for Ca2+ channel blockers? |
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Definition
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Term
| What 3 drug action sites have to do with vesicles? |
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Definition
Secretory vesicle/plasma fusion process
Vesicular DA transporter
(SNAP OMPs involved in vesicular exocytosis) |
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Term
| What presynaptic enzyme can be a target for drugs? |
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Definition
| Tyrosine Hydroxylase => rate limiting enzyme for neuronal NE synthesis |
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Term
| What is the drug target site aimed at intrecaellular organelles? |
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Definition
| Inhibition of mitochondrial MAO => increase presynaptic NE |
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Term
| What 2 things can drugs add to the synaptic cleft as an action? |
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Definition
Exogenous NE (or similar agonist)
Receptor antagonist |
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Term
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Definition
1) Post-synaptic adrenoreceptors
2) Pre-synaptic auto receptors
3) Non-adrenergic post-synaptic receptors
4) Non-adrenergic presynaptic receptors
5) Presynaptic NE transporter
6) Secretory vesicle/plasma membrane fusion process
7) Tyrosine Hydroxylase
8) Ca2+ Channel
9) Vesicular Dopamine Transporter
10) SNAP proteins
11) Inhibition of mitochondrial MAO
12) Add exogenous NE (or other agonists)
13) Add receptor antagonists. |
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Term
Function:
Nicotinic acetyl choline receptor |
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Definition
| gates a sodium channel to produce depolarization in skeletal muscle |
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Term
| Function: Muscarinic acetylcholine receptor |
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Definition
| activate biochemical pathway to increase intrecellular Ca2+ in smooth muscles |
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Term
Function:
β-adrenergic receptor |
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Definition
| Binds epi & activates an increase in cAMP in many cell types |
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Term
Function:
Insulin receptor |
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Definition
| Activate recruitment of GLUT4 glucose transporter molecules to the plasma membrane of many cells |
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Term
Function:
Glucocorticoid receptor |
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Definition
| translocates from cytoplasm to nucleus to turn on transcription of specific genes |
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Term
| How does the anti-tumor drug adriamycin inhibit transcription? |
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Definition
| Intercalation into the DNA minor groove |
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Term
| How do statins inhibit cellular cholesterol biosynthesis? |
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Definition
| Bind to HMG-CoA reductase |
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Term
| Where does α1-adrenoreceptor signal? |
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Definition
| Arteriolar smooth muscle =>contraction |
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Term
| What signal molecule is released from a sympathetic nerve terminal in α1-adrenergic stimulation? |
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Definition
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Term
| What does the singal molecule, NE, bind to in α1-adrenergic stimulation? |
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Definition
| Arteriolar smooth muscle plasma membrane α1-adrenoreceptor |
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Term
| What does NE binding to α1-adrenoreceptor do to the receptor? |
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Definition
| Induces a conformational change in the receptor protein. |
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Term
| What does the conformational change of the α1-adrenoreceptor allow? |
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Definition
| Intracellular part of the receptor to catalyze the exchange of GDP with GTP on α subunit of Gq |
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Term
| What happens once the α subunit of Gq is phosphorylated to GTP in α1-adrenergic signaling pathway? |
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Definition
Allows: Gq βγ subunits dissociate
Activates: Phospholipase Cβ to breakdown PIP2 => releases IP3 & DAG |
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Term
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Definition
| gated channel to release intracellular Ca2+ |
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Term
| What activates PKC (Protein Kinase C)? |
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Definition
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Term
| What does activated PKC do? |
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Definition
| Allows entry of extracellular Ca2+ => muscle contraction. |
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Term
| What does it mean that binding of ligands to receptor is controlled by mass action? |
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Definition
| Increasing ligand concentration produces more binding, but there is a limit - a saturation point beyond which there is no further binding. |
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Term
| What is the equilibrium equation for drug & receptor? |
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Definition
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Term
| What is the equation for the equilibrium dissociation constant for drug & receptor? |
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Definition
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Term
| What is kon?
What is koff? |
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Definition
k on = forward rate constant
k off = reverse rate constant |
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Term
| What does magnitude of response of a drug depend on? |
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Definition
| binding of receptors, therefore response=max response when [DR] = [R]total (when all DR is formed) |
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Term
Equation
Response/Max Response |
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Definition
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Term
| When isn't binding of DR:response 1:1? |
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Definition
| Signaling systems where downstream effects are amplification. |
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Term
| How is Kd similar to Km in kinetics? |
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Definition
| Just like Km = concentration where 1/2 receptors are occupied, Kd = concentration where 1/2 receptors are occupied. |
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Term
What plot types are used for plotting over a larger concentration range?
Why would we need to do this? |
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Definition
logarithmic plots
to compare drugs |
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Term
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Definition
| a ligand that binds to a receptor to directly activate a signaling pathway. |
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Term
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Definition
| stablize receptor in a particular conformation |
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Term
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Definition
| measure of the maximum response obtained with the highest concentrations of the agonist. |
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Term
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Definition
| Measure of the concentration of agonist required to achieve 50% of maximum response |
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Term
| What is EC50 usually equivalent to? |
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Definition
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Term
| What is used to compare 2 agonists for the same receptor? |
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Definition
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Term
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Definition
| Comparison of EC50 values for 2 or more agonists.
It compares the concentrations needed for 50% response. |
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Term
| When does a drug have greater potency? |
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Definition
| When EC50 is smaller, i.e. smaller concentration is needed to get desired response. |
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Term
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Definition
| drugs that produce an effect with lower efficacy than the standard full agonists. |
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Term
| How can compounds such as atropine with zero efficacy be useful? |
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Definition
| Can antagonize the binding & therefore the biological actions of agonists. |
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Term
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Definition
| an agent that binds to a receptor but cannot produce the conformational change necessary to trigger the downstream events. |
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Term
| What response is seen when an antagonist is bound by itself? |
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Definition
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Term
def
competetive antagonist |
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Definition
| an antagonist that binds reversibly therefore can be competed away by higher agonist concentrations. |
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Term
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Definition
| when an antagonist binds to its receptor, it "blocks" further binding of an agonist => hindering ability to activate receptor. |
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Term
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Definition
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Term
| What happens to the concentration-response curve for an agonist with increasing concentrations of competitive antagonist? |
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Definition
| EC50 gets pushed to the right, but there's no change in efficacy. |
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Term
| What is the equation for the response for competitive antagonism? |
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Definition
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Term
def
non-competitive antagonist |
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Definition
| antagonist that either inactivate the receptor molecules or else act on a downstream site |
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Term
| What happens to the concentration-response curve for an agonist with a non-competitive antagonist? |
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Definition
| decrease efficacy.
no effect on EC50 |
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Term
| Will increasing concentrations of agonist overcome a non-competitive antagonist? |
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Definition
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Term
| What is the equation for the response for non-competitive antagonism? |
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Definition
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Term
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Definition
Since enzymes can amplify a signal, not 100% of the receptors need to be used to produce max response.
The remaining unoccupied receptors are the spare receptors. |
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Term
| What is the advantage to spare receptors? |
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Definition
| activation at low concentrations with faster turn off. |
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Term
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Definition
produces a response opposite that of an agonist.
(unlike antagonist when alone produces no response) |
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Term
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Definition
diffusion rate.
(it's fairly constant for sm. ligands) |
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Term
| What determines the magnitude of KD? |
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Definition
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Term
| What happens when koff is small? |
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Definition
| KD is small => high affinity binding |
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Term
| What happens when koff is large? |
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Definition
| KD is large => low affinity binding |
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Term
| When will there be a faster release of ligand when concentration drops? |
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Definition
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Term
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Definition
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Term
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Definition
| Non-competitive Antagonist |
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Term
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Definition
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Term
| How can you change the potency, efficacy, and/or change an agonist to an antagonist? |
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Definition
| Changing substituent groups around the core structure of a compound. |
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Term
| How are congeners produced? |
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Definition
| Adding on longer hydrocarbon chains. |
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Term
| How are analogs produced? |
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Definition
| A substitution of an esteric linkage. |
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Term
| What are analogs often useful in producing? |
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Definition
| Longer-lived version of an endogenous compound. |
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