Medicinal ChemistryLecture 8

Exam Revision

Receptors and Receptor Site

Continue…• Receptor down-regulation:A phenomenon whereby an agonist, after binding

to a receptor, actually induce a decrease in the number of these receptors available for binding

• Receptor Up-regulation:The opposite of the above, involves an agonist-

induced increase in the number of receptors.

Continue…• Affinity:The ability of the drug to combine with a receptor.

A ligand of low affinity requires a higher concentration to produce the same effect as a ligand of high affinity. Both agonists and antagonists have affinity for the receptor.

Efficacy:Describe the relative intensity with which agonist

vary in the response they produce when occupying the same number of receptors and with the same affinity

Continue…• Potency:Refers to the dose of a drug required to produce

effect of given magnitude as compared to a standard reference. Potency is dependent on both affinity and efficacy.

• Tolerance: Decrease of the intensity of the response to a

given dose over time

Stereochemistry of Drug Action

Structurally Rigid Groups

The influence of configuration on ADME•Absorption:

Active Transport:• (-)Norgestrel is absorbed at twice the rate of

(+)Norgestrel• L-Dopa is more rapidly absorbed in comparison

to D-Dopa

• Passive diffusion:• No difference in absorption between

enantiomers

• Racemates may be absorbed at a rate that is different to their pure individual enantiomers

Distribution• Stereoselectivity appears to have little influence

on the transport of stereoisomers through the circulatory system.

• Some enantiomers prefer to bind to a specific plasma protein (R-Propanalol prefers to bind to human albumin while S-Propanalol prefers alpha-acid glycoproteins)

Metabolism

• S-Indacrinone plasma half-life is 2-5 hours• R-Indacrinone plasma half-life is 10-12 hours

Extraction• Modest stereoselectivity has been reported in

the renal excretion of these drugs

Next Lecture

•Drug Metabolism

THE END