Core5: Receptor theory - agonist, partial agonist, antagonist, inverse agonist

🧬 High-yield / 要点：Agonists increase receptor response; antagonists block agonists; partial agonists have lower Emax and can functionally antagonize full agonists; inverse agonists reduce constitutive activity.

Agonist vs antagonist / 作動薬と拮抗薬

Drug type	Effect after binding	Efficacy	Example
Full agonist	Activates receptor and produces maximal response	Maximal Emax	Norepinephrine
Partial agonist	Activates receptor but cannot reach maximal response	Lower Emax	Buprenorphine at μ-opioid receptor
Pure/neutral antagonist	No response by itself; blocks agonist binding/action	Zero intrinsic efficacy	Bisoprolol; flumazenil at benzodiazepine receptor
Inverse agonist	Stabilizes inactive receptor state and decreases basal activity	Negative effect vs constitutive activity	Classically may appear as antagonist if no constitutive activity is considered

Partial agonist / 部分作動薬

• Produces submaximal response even at high concentration.
• In presence of a full agonist, it can displace the full agonist and reduce total response.
• Therefore, a partial agonist can behave like an antagonist against a full agonist.

Two-state receptor model / 二状態受容体モデル

• Receptor has two conformations:
  • Ra：active state.
  • Ri：inactive state.
• Even without ligand, some receptors may show constitutive activity.
• Agonist binds/stabilizes Ra → response increases.
• Neutral antagonist binds both states similarly → blocks agonist but does not change basal activity.
• Inverse agonist stabilizes Ri → decreases constitutive activity.

Types of antagonism / 拮抗の種類

• Competitive antagonism：agonist and antagonist compete at the same binding site.
  • Typical effect: dose-response curve shifts right.
• Non-competitive antagonism：
  • Allosteric：binds different site on same receptor.
  • Functional：two agonists act on different receptors with opposite physiological effects.
  • Example: epinephrine vs acetylcholine on heart rate.
• Irreversible antagonism：permanently prevents activation.
  • Example: aspirin irreversibly inhibits COX.

Remember / 覚え方

• Full agonist = full Emax
• Partial agonist = lower Emax + can block full agonist
• Antagonist = blocks without activating
• Inverse agonist = below baseline