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Published bySucianty Widjaja Modified over 5 years ago
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Full agonists The “agonists” referred to so far are FULL AGONISTS
Able to produce a maximum response for the tissue Even though only a fraction of the receptors are occupied
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Curve for a full agonist
100 75 % Maximum response Typical curve for a full agonist 50 25 0.001 0.01 0.1 1 10 100 log conc (µM)
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Curves for Full agonist and Partial agonist
100 75 % Maximum response PARTIAL 50 25 0.001 0.01 0.1 1 10 100 log conc (µM)
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Relationship between occupancy and response
FULL 100 80 60 PARTIAL Response (% maximum) 40 20 ANTAGONIST 0.0 0.2 0.4 0.6 0.8 1.0 Fractional occupancy
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Differences between Full and Partial agonists
FULL agonist - produces maximum response even when only a FRACTION of receptors are occupied PARTIAL agonist - CANNOT produce a maximum tissue response even when ALL receptors are occupied Note the curves are not parallel
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Why is there a difference?
The reason is due to EFFICACY Full agonists are said to have a higher efficacy than partial agonists What is efficacy? The ability of the drug-receptor complex to produce a response In other words how well a drug produces an effect - IN A PARTICULAR SYSTEM i.e. can vary tissue to tissue - even when the RECEPTORS are the SAME
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Mathematical explanation
Response depends upon characteristics of the TISSUE characteristics of the DRUG Response = ƒ Ntot XA XA + Kd ƒ (transducer function) Ntot (number of receptors) Kd (dissociation constant) (intrinsic efficacy) ( ) } Properties of the TISSUE } Properties of the DRUG
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Inverse agonists Do not confuse with an antagonist!!!
Receptors can exist in 2 conformational states –”2 state model” These are “resting” and “activated” Agonists, antagonists and inverse agonists have differing binding affinities to these states
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Two-state model R R* Inverse agonist Agonist resting activated
RESP resting activated Antagonist
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Recommended Reading Agonists
Medical Pharmacology at a Glance, 5th Ed: Page 11 Pharmacology, 5th Ed: Pages 11-14 Basic and Clinical Pharmacology Online Book: Section I, Chapter 2, Relation between drug concentration and response, Partial Agonists
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