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Related Concept Videos

Quantitative Aspects of Drug-Receptor Interaction01:30

Quantitative Aspects of Drug-Receptor Interaction

The receptor occupancy theory connects a drug's response to the number of occupied receptors. With higher drug concentrations, more receptors are occupied, leading to increased responses. The formation of drug-receptor complexes involves association and dissociation rates, which reach equilibrium when the forward and backward reactions are equal. The equilibrium association constant (Ka) and its inverse, the equilibrium dissociation constant (Kd), indicate drug affinity. Higher Ka and lower Kd...
Spare Receptors01:30

Spare Receptors

Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...
Dose-Response Relationship: Overview01:03

Dose-Response Relationship: Overview

Agonists can bind with and activate receptors, resulting in the formation of drug-receptor complexes. Once formed, these complexes catalyze many biochemical processes at the cellular level and subsequently induce a pharmacologic response. The degree of response is directly proportional to the fraction of activated receptors, which in turn, depends on the concentration of the drug at the receptor site as well as the sensitivity of the receptor. An increase in the administered dose contributes to...
Drug-Receptor Interaction: Agonist01:25

Drug-Receptor Interaction: Agonist

Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
Drug-Receptor Interactions01:29

Drug-Receptor Interactions

Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue.
Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
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Updated: Jun 6, 2026

A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
07:51

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Published on: June 18, 2018

Absolute Receptor Occupancy, Not Rate of Decline, Predicts Relapse.

Robert A McCutcheon1,2,3, Toby Pillinger1,2,4, Jose M Rubio5

  • 1Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.

Schizophrenia Bulletin
|June 4, 2026
PubMed
Summary
This summary is machine-generated.

Antipsychotic relapse risk after stopping medication is linked to dopamine D2 receptor occupancy, not the speed of decline. Gradual tapering does not significantly lower relapse risk compared to abrupt discontinuation.

Keywords:
antipsychoticclinical trialsdiscontinuationpsychosisrelapseschizophrenia

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Area of Science:

  • Psychiatry
  • Neuroscience
  • Pharmacology

Background:

  • Relapse following antipsychotic discontinuation is a significant clinical challenge.
  • Dopamine D2 receptor occupancy is associated with relapse, but the role of discontinuation speed is debated.

Purpose of the Study:

  • To evaluate whether the speed of antipsychotic dose reduction or tapering schedule influences relapse risk.
  • To determine if relapse risk is primarily driven by withdrawal kinetics or falling below a therapeutic threshold.

Main Methods:

  • Meta-analysis of discontinuation studies comparing abrupt versus gradual tapering.
  • Review of existing trial data on relapse rates across different discontinuation arms.
  • Analysis of the relationship between antipsychotic dose, receptor occupancy, and relapse risk.

Main Results:

  • No significant difference in relapse risk between abrupt and gradual antipsychotic discontinuation.
  • Apparent advantages of slower dose reduction may reflect continued therapeutic exposure, not tapering effects.
  • Relapse risk appears determined by falling below a therapeutic threshold, not withdrawal kinetics.
  • Early relapse can occur even during maintenance treatment and does not resemble a withdrawal syndrome.

Conclusions:

  • The tapering schedule does not independently reduce relapse risk after antipsychotic discontinuation.
  • Relapse is primarily determined by antipsychotic exposure falling below a therapeutic threshold.
  • While gradual discontinuation may have practical benefits, robust evidence for its independent effect on reducing relapse risk is lacking.