Positron Emission Tomographic Analysis of Central D1 and D2 Dopamine Receptor Occupancy in Patients Treated With Classical Neuroleptics and Clozapine

Raclopride and Chlorpromazine, but not Clozapine, Increase Muscle Rigidity in the Rat Relationship with D2 Dopamine Receptor Occupancy

“…Support for the view that there may be an association between the appearance of extrapyramidal side effects and D 2 receptor occupancy has come from positron emission tomography (PET) studies in humans (Farde and Nördström 1992a;Farde et al 1992b Farde et al , 1992cNyberg et al 1995). These studies showed that EPS were associated with high D 2 receptor occupancy of 70%-89% in the striatum obtained with conventional doses of typical antipsychotics, but showed no association with D 1 occupancy.…”

“…These studies showed that EPS were associated with high D 2 receptor occupancy of 70%-89% in the striatum obtained with conventional doses of typical antipsychotics, but showed no association with D 1 occupancy. Importantly, clozapine whose (Farde and Nörd-ström 1992a;Farde et al 1992b Farde et al , 1992cNyberg et al 1995).…”

“…These studies showed that EPS were associated with high D 2 receptor occupancy of 70%-89% in the striatum obtained with conventional doses of typical antipsychotics, but showed no association with D 1 occupancy. Importantly, clozapine whose (Farde and Nörd-ström 1992a;Farde et al 1992b Farde et al , 1992cNyberg et al 1995).Despite being the subject of intense research interest, the mechanisms underlying drug-induced EPS remain unknown. One of the main factors contributing to this situation has been the lack of an objective, quantifiable experimental endpoint relevant to a cardinal feature of EPS, muscle rigidity, or increased muscle tone.…”

Evaluation of N-Desmethylclozapine as a Potential Antipsychotic—Preclinical Studies

“…As compared to other antipsychotics, clozapine shows two unique abilities; a very low propensity for extrapyramidal symptoms (EPS) and efficacy in patients for whom other typical and atypical drugs have not been effective. There are several accounts for its freedom from EPS: low affinity for and low occupancy of D 2 receptors, 5-HT 2 antagonism, cholinergic effects, and 5-HT 1A agonism (Meltzer et al, 1989;Farde et al, 1992;Rollema et al, 1997;Bymaster et al, 2003). However, the reason for its unique therapeutic efficacy is still not well understood.…”

Effects of Atypical Antipsychotic Drug Treatment on Amphetamine-Induced Striatal Dopamine Release in Patients with Psychotic Disorders

“…We did not examine the effects of traditional neuroleptic treatment on amphetamine-induced raclopride binding to determine if classical antipsychotic agents and atypical drugs have differential striatal dopamine effects. Therapeutic doses of traditional antipsychotic agents show a steep dose-occupancy curve with apparent near-maximal binding of striatal D-2 receptors (i.e., у 80% estimated occupancy) (Farde et al 1988(Farde et al , 1992Wiesel et al 1990;Pilowsky et al 1993;Wolkin et al 1989;Coppens et al 1991;Karbe et al 1991) which could lead to baseline raclopride binding ratios that are too low to adequately assess amphetamine-related reductions in ligand binding. Another important issue is the lack of dopamine release data from A-10 dopamine neurons in limbic and cortical areas.…”