third year lecture 8
TRANSCRIPT
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