10- Pharmacodynamics Part II (6.22.26)

PBSI 336:

Drugs & Behavior

Summer 2026

1.2. Introduction:Current drug use trends, history of drug policy

Professor: Morgan Paladinomsp@tamu.eduDepartment of Psychological & Brain Sciences

6.1.2026

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Don’t forget your Exit Ticket: tx.ag/drugsandbehavior

Summary

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• Drug-receptor interactions
• Law of mass action
• Reversibility
• Dose-response curves
• ED, TD, LD, therapeutic index
• Potency & efficacy
• Agonists & antagonists
• Antagonists: competitive and non-competitive
• Agonists: full, partial, inverse
• Drug experience: Dependence and withdrawal
• Drug experience: Tolerance and sensitization
• Characteristics
• Mechanisms: metabolic, pharmacodynamic, behavioral
• Role of conditioning and context

Dose-response functions

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Potency = amount of drug needed to produce an effect. Efficacy = maximum effect that can be produced by a drug.

Example: For measures of pain management, all these drugs have different potency, but the opioids (hydromorphone, morphine, and codeine) have similar efficacy.

Why do some drugs have higher potency than others?

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Parallel curves/slopes suggest that the same receptor is involved. But, drugs may have different binding affinity for those receptors. Binding affinity does not determine the maximum possible effect, because at high doses, lots of drug molecules are available to take the place of those that dissociate.

Why do some drugs have higher efficacy than others?

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They may act by different mechanisms (e.g., different receptors). example: morphine vs. aspirin (opioid receptors vs. COX enzymes) They may have different activity at the same receptor, once bound. example: morphine vs. buprenorphine (full agonist vs. partial agonist)

Agonists and antagonists

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Subtitle

Antagonists Competitive, non-competitive

Agonists Full, partial, inverse

Agonists and antagonists

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Antagonists Competitive, non-competitive

Agonists Full, partial, inverse

https://ditki.com/course/pharmacology/pharmacokinetics/pharmacodynamics/1638/agonists-antagonists/notes

Competitive antagonists

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Example: Naloxone (Narcan ©) is a competitive antagonist for opioid receptor with high binding affinity; used to treat heroin overdose.

• Competitive antagonists bind to same receptor binding site as agonist (the antagonist “competes” for available binding sites).
• Antagonist effect can be overcome by adding more of the agonist.
• Shifts dose-response for agonist to the right.

https://ditki.com/course/pharmacology/pharmacokinetics/pharmacodynamics/1638/agonists-antagonists/notes

Non-competitive antagonists

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• Non-competitive antagonists do not compete with agonist for receptor binding site (e.g. may bind to another site on receptor).
• Antagonism cannot be overcome by more of the agonist - there is a decrease in maximum effect.
• Shifts the dose-response curve for agonist to the right, but also change its shape.

Example: PCP is a non-competitive antagonist at glutamate NMDA receptors; it binds in a different location than glutamate.

https://ditki.com/course/pharmacology/pharmacokinetics/pharmacodynamics/1638/agonists-antagonists/notes

Partial agonists

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• Efficacy of partial agonist is lower than full agonist, higher than antagonist.

• In the presence of full agonists, they can act as antagonists (by competing with the full agonists for binding sites).

Example: Buprenorphine A long-acting opioid partial agonist used for analgesia and opioid addiction therapies. More potent than methadone for analgesia (due to high affinity) but less efficacy for getting “high”. Will act as antagonist to methadone if administered together.

Inverse agonists

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• Inverse agonists bind to receptor, initiate cellular response opposite to agonist.
• Descending dose-response curve.

Note the difference between antagonists and inverse agonists. Antagonists act by interfering with the effects of agonists (whether drugs or endogenous ligands).

https://ditki.com/course/pharmacology/pharmacokinetics/pharmacodynamics/1638/agonists-antagonists/notes

Receptor agonists, antagonists, partial agonists, and inverse agonists

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Allosteric modulators

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Allosteric modulators are ligands/drugs that indirectly influence the effects of a primary ligand via actions at a separate binding site; no direct effects.

• Positive allosteric modulators (PAMs) amplify primary ligand effects.
• Negative allosteric modulators (NAMs) reduce primary ligand effects (a.k.a. noncompetitive antagonists).

Example: Benzodiazepines act as PAMs at the GABAA receptor and enhance GABA-induced opening of chloride channel.

Agonists and antagonists

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Antagonists Competitive, non-competitive

Agonists Full, partial, inverse

Thanks for listening!

Don’t forget your Exit Ticket: tx.ag/drugsandbehavior

45

Thanks for listening!

Don’t forget your Exit Ticket: tx.ag/drugsandbehavior

Next class:

3.2. The nervous system: Receptor signaling