Quantitative Arguments for the Existence of Drug Receptors and the Development of the Receptor Occupancy Theory, c. 1910–60

2009 ◽  
pp. 107-124
Author(s):  
Cay-Rüdiger Prüll ◽  
Andreas-Holger Maehle ◽  
Robert Francis Halliwell
Keyword(s):  
Receptor Occupancy ◽  
Drug Receptors

Estimation of receptor occupancy and synaptic dopamine after amphetamine challenge: A competition model approach

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S613-S613
Author(s):  
Hiroto Kuwabara ◽  
Anil Kumar ◽  
James Brasic ◽  
Ayon Nandi ◽  
Dean F Wong
Keyword(s):  
Receptor Occupancy ◽  
Competition Model ◽  
Model Approach

A Simple and Rapid Method to Determine GPIIb/IIIa-Receptor Inhibitor Activity in Whole Blood

1999 ◽  
Vol 19 (03) ◽  
pp. 134-138
Author(s):  
Gitta Kühnel ◽  
A. C. Matzdorff
Keyword(s):  
Flow Cytometry ◽  
Platelet Count ◽  
Blood Sample ◽  
Platelet Activation ◽  
Whole Blood ◽  
Receptor Occupancy ◽  
Aggregate Formation ◽  
Inhibitor Activity ◽  
Receptor Inhibitor

SummaryWe studied the effect of GPIIb/IIIa-inhibitors on platelet activation with flow cytometry in vitro. Citrated whole blood was incubated with increasing concentrations of three different GPIIb/IIIa-inhibitors (c7E3, DMP728, XJ757), then thrombin or ADP were added and after 1 min the sample was fixed. Samples without c7E3 but with 0.1 U/ml thrombin had a decrease in platelet count. Samples with increasing concentrations of c7E3 had a lesser or no decrease in platelet count. The two other inhibitors (DMP 725, XJ757) gave similar results. GPIIb/IIIa-inhibitors prevent aggregate formation and more single platelets remain in the blood sample. The agonist-induced decrease in platelet count correlates closely with the concentration of the GPIIb/IIIa inhibitor and receptor occupancy. This correlation may be used as a simple measure for inhibitor activity in whole blood.

Pharmacokinetics and dopamine d2 and serotonin 5-ht2a receptor occupancy of paliperidone in healthy subjects: two open-label, single-dose studies (PAL-115)

2007 ◽  
Vol 40 (05) ◽  
Author(s):  
P Karlsson ◽  
L Hargarter ◽  
E Dencker ◽  
S Nyberg ◽  
E Mannaert ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Subjects ◽  
Receptor Occupancy ◽  
Open Label ◽  
Dopamine D2

P.2.085 Visualisation of dopamine-2 receptor occupancy in psychotic patients treated with olanzapine, risperidone, clozapine and haloperidol

1997 ◽  
Vol 7 ◽  
pp. S219
Author(s):  
J. Tauscher ◽  
B. Küfferle ◽  
C. Barnas ◽  
S. Asenbaum ◽  
Th. Brücke ◽  
...  
Keyword(s):  
Receptor Occupancy ◽  
Dopamine 2 Receptor

scholarly journals High dose antipsychotic polypharmacy and dopamine partial agonists - time to rethink guidelines?

2021 ◽  
pp. 026988112110264
Author(s):  
Gavin P Reynolds
Keyword(s):  
Side Effects ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Receptor Site ◽  
Receptor Occupancy ◽  
Antipsychotic Agents ◽  
High Dose ◽  
Partial Agonists ◽  
Favourable Side Effect Profile ◽  
Different Characteristics

Guidelines for the treatment of schizophrenia limit the use of antipsychotic agents to clinically-established maximum doses. This acknowledges both the absence of additional efficacy of dopamine D2 receptor antagonists above a receptor occupancy threshold, and the increases in side effects that can occur at higher doses. These limits restrict the dosing of combinations of antipsychotics as they do single agents; drugs sharing the major antipsychotic mechanism of D2 receptor antagonism will act additively in blocking these receptors. Several newer antipsychotic drugs, including aripiprazole and cariprazine, act as partial agonists at the D2 receptor site and avoid action at several other receptors, effects at which are responsible for some non-dopaminergic adverse effects. This pharmacology imparts different characteristics to the drugs resulting often in a more favourable side effect profile. Their partial agonism, along with high affinities for the D2 receptor, also means that these drugs given adjunctively may in part replace, rather than enhance, the D2 antagonism of other antipsychotic agents. This can result in an improvement in certain side effects without loss of antipsychotic efficacy. This article makes the case for distinguishing the D2 partial agonists from antagonists in defining maximum doses of combined treatments, which would increase the options available to the prescriber, emphasising that pharmacological mechanisms need to be understood in identifying optimal treatments for psychotic illness.

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