Markers of D(2) and D(3) receptor activity in vivo: PET scan and prolactin.
Positrons Emission Tomography (PET) allows to evaluate the dopaminergic activity of antipsychotic, by measuring post synaptic D(2) dopaminergic receptors occupancy. A good correlation was brought forward between a rate of occupancy of 80% of striatal D(2) receptors and the occurrence of extrapyramidal effects. These PET studies have also established that at least 60% D(2) receptors occupancy was predictive of clinical antipsychotic response. The PET studies in healthy volunteers can then be used to help choose doses to be tested during the clinical trials of new antipsychotic drugs. The increase in prolactin level is one other of the markers of the antagonist dopaminergic activity which concerns D(2) receptors of the pituitary gland. The example of S 33138, a potential antipsychotic, preferential D(3) versus D(2) receptor antagonist will be given to illustrate these data. The results of two PET studies as well as the effects on prolactin and extrapyramidal signs will be presented.
Thomasson-Perret
Nitza
N
Institut de Recherches Internationales Servier, Courbevoie, France.
Pénélaud
Pierre-François
PF
Théron
David
D
Gouttefangeas
Sylvie
S
Mocaër
Elisabeth
E
D000083:Acetanilides / Q000493:pharmacokinetics; D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001578:Benzopyrans / Q000493:pharmacokinetics; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D006801:Humans; D049268:Positron-Emission Tomography; D011388:Prolactin / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000187:drug effects / Q000378:metabolism*
D000083:Acetanilides; D014150:Antipsychotic Agents; D001578:Benzopyrans; D018492:Dopamine Antagonists; C526614:N-(4-(2-(8-cyano-1,3a,4,9b-tetrahydro(1)benzopyrano(3,4-c)pyrrol-2(3H)-yl)ethyl)phenyl)acetamide; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011388:Prolactin