Buxton: receptor theory Flashcards
(57 cards)
main targets of drugs (4)
think TIER
- -enzymes (aspirin, cyclooxygenase)
- -transporters/carriers (prozac, serotonin reuptake transporter)
- -ion channels (local anesthetics + Na+ channels)
- -receptor proteins (cimethidine for histadine receptor)
(drug, target)
“receptor”
PROTEIN that participates in cellular communicatin via chemical signals
ligand
chemical signaling molecule that transmits signal to biochemical change in target
ligand examples (just throw a few out there)
drugs or hormones and NT
Receptor theory equation
D + R –> DR —> Effect
drug, receptor, drug-receptor complex
mass action
rate of RXN proportional to the product of concentration of reactants
JUST THINK LE CHATERLIER’S
hill langmuir equationa
[D] + [R] [DR]
k1=forward rxn
k-1= reverse rxn
Radioreceptor/radioligand binding assay
[receptor prep + radiolabeled drug + test drug] get put into test tube. then placed into a drug receptor complex, filtrated, and unbound drug or unbound radiolabeled drug get eluted off.
PURPOSE: figure out Kd/KA
kinetic experiment (radiolabeled)
look at K1 and K2 over time by looking at specific binding (counter per minute). K1 in mol/sec. k2 in sec.
total binding line
specific binding + non specific binding binding curves. add areas under curves
specific binding line
it’s linear and strong but then it tapers off, kinda looks the the Vmax line
non specific binding
binding to places OTHER than the THERAPEUTIC target. This line is linear so directly propertional to ligand added
Hyperbolic concentration binding curve
Drug concentration binding curve (x-axis) vs fraction of receptor bound [B] y axis.
Kd=when half of the receptors are bound (same thing as Ka)
Bmax = just Kmax but for binding (rectangular hyperbola).
Scatchard plot
specific binding/ free radioligand (y axis) vs specific binding (x axis).
B max is the x intercept
slope = -1/Kd
if specific binding, then LINEAR line
Hill-Langmuir equation
Background just to help out: Kd= k-1/k1; it’s a concentration. also known as dissociation constant.
Par = [D][[D] + Kd]]
where AR = DR
SUPER LEGIT TO FIGURE OUT PROPORTION OF DR/AR
log linear scale
y axis; fraction of receptor bound, B.
x axis: concentration in log scale.
overall: graph sigmoidal, and it’s easy to see the Kd; this means that drug is acting well
ED50
TD50
LD50
therapeutic effect (dose) toxic effect (dose) lethal (dose) at which 50 percent of ppl are affected
What’s the difference between graded concentration response curves and hyperbolic concentration binding curve?
y axis: %maximal response v fraction of bound
graded concentration response curve similarities to binding curve?
x axis: concentration in same units
GRAPH shape rectangular hyperbola in both
Quantal dose response curve
describe pop % responding rather than individual responses. in log scale and helps us identify best dosage
Full Agonist: two cases
max potency and MAX EFFECT
other case, reduced potency but MAX EFFECT
Partial Agonist
max potency but REDUCED EFFECT.
other casse, reduced potency but REDUCED effect
Potency
deterimined by concentration needed for effect
What determines whether or not something is a full or partial agonist?
If the effect% is close to 100, then it’s full.
If effect% is low (close to 50%), then it’s partial
