Question

Briefly outline an experiment that would determine the relative potencies of two agonists acting at different receptors e.g. carbachol and serotonin

Answer 1

An agonist can be defined as a drug which binds to a receptor and activates it, producing a pharmacological response (contraction, relaxation, secretion, enzyme activation, etc.). The term potency is used as a comparative term for distinguishing which agonist has a higher affinity for a given receptor. The drug which can produce an effect at lower drug concentrations is “more potent”. Relative potency can be defined as the ratio of the potency of a test drug (i.e. its EC₅₀, IC₅₀, etc.) to that of a standard drug.

Experimental design:

• Carbachol and serotonin have muscarinic receptors. Tissues that have receptors for these agonists have to be chosen, such as tissues from CNS and ganglia in the case of carbachol and serotonin.
• The tissues should be allowed to react with the standard agonist at different concentrations so as to record the slight, moderate, and marked effects.
• The first agonist should be allowed to act on the first tissue for 5 min
• The tissue strip should be washed thoroughly
• The second agonists should then be allowed to act for 5-6mins
• The concentrations of agonists should be chosen in a way that the responses should roughly match those produced by a standard and a calculation similar to that used in a 4-point assay.
• The result can be expressed as an equipotent molar ratio relative to the standard: this will be less than I if the compound is more active than the standard and greater than 1 if it is weaker.

Estimates of the log equipotent molar ratio relative to standard on tissue 1 at a certain temperature like 37^oC plotted against the log equipotent molar ratio relative to standard on tisue 2 at the same temperature.