D3-receptor

FIGURE 5.1 Ratio of affinity (open circles) and agonist potency (filled circles) for dopamine agonists on dopamine D2 vs D3 receptors. Abscissae numbers referring to agonist key on right. Data calculated from [1],... 

Dopamine D2 receptors are involved in some emetic responses but studies have also suggested that activation of D3 receptors in the area postrema may either produce vomiting or enhance that elicited by D2 receptor activation. 

The retinoid X receptor (RXR) is a nuclear receptor that binds and is activated by certain endogenous retinoids, such as 9-cis-retinoic acid. RXR is the obligatory heterodimerization partner for a large number of nonclassic steroid nuclear receptors, such as thyroid hoimone receptor, vitamin D3 receptor, peroxisome proliferator-activated receptor and pregnane X receptor. 

G Protein-Coupled Receptors (GPCRs) ttiA Adrenergic Receptor Dopamine D3 Receptor Endothelin A Receptor... 

Amisulpride is a substituted benzamide, which acts as a highly selective blocker of D2 and D3 receptors (Kerwin, 2000). As with all the other drugs, it can easily be demonstrated to be effective compared with placebo and haloperidol, with a lower extrapyramidal symptom profile (Moller et al, 1995). The strength of amisulpride lies in the quality of the evidence to show that it is effective against primary negative symptoms and affective symptoms. Two studies have shown convincing superiority for negative symptoms... 

As with many neurons (e.g. NA) there are presynaptic autoreceptors on the terminals of dopamine neurons whose activation attenuate DA release. Although most of these receptors appear to be of the D2 type, as found postsynaptically, D3 receptors are also found. It is possible that in addition to the short-term control of transmitter release they may also be linked directly to the control of the synthesising enzyme tyrosine hydroxylase. It seems that autoreceptors are more common on the terminals of nerves in the nigrostriatal (and possibly mesolimbic) than mesocortical pathway. 

The receptor mediating all three effects appears to be the D2 (or D3) receptor. 

Among the D2 family of receptors (D2, D3 and D4) the D2 receptor itself seems to be the most important. At a therapeutic concentration, most neuroleptics, except clozapine (and risperidone), should, according to in vitro binding studies, be occupying 50-70% of brain D2 receptors. The picture is similar for D3 receptors but only clozapine (and... 

There are few specific drugs for D3 receptors but D3 knock-out mice show no behavioural defects. Thus the significance of any DA receptor other than the D2 still remains to be established (see Seeman and Van Tol 1994 Sokoloff and Schwartz 1995 Strange 1994). 

Yokoi, F. et al. (2002). Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597) a study using positron emission tomography and (llC)raclopride. Neuropsychopharmacology, 27, 248-59. 

Scharfetter, J., Chaudhry, H. R., Hornik, K. etal. (1999). Dopamine D3 receptor gene polymorphism and response to clozapine in schizophrenic Pakistani patients. Eur. Neuropsychophar-macol., 10, 17-20. 

Laszy J, Laszlovszky I, Gyertyan I. Dopamine D3 receptor antagonists improve the learning performance in memory-impaired rats. Psychopharmacology (Berl) 2005 179 567-575. 

Gurevich, E. V. Joyce, J. N. (1999). Distribution of dopamine D3 receptor expressing neurons in the human forebrain comparison with D2 receptor expressing neurons. Neuropsychopharmacology 20, 60-80. 

Clemens S., Hochman S. (2004). Conversion of the modulatory actions of dopamine on spinal reflexes from depression to facilitation in D3 receptor knock-out mice. J. Neurosci 24, 11337-45. 

Hue G Decker M., Solomon L, Rye D. (2003). Increased wakefulness and hyper-responsivity to novel environments in mice lacking functional dopamine D3 receptors. In Society for Neuroscience. 

Le Foil, B., Diaz, J., Sokoloff, P. Increased dopamine D3 receptor expression accompanying behavioral sensitization to nicotine in rats. Synapse. 47 176, 2003. 

Le Foil, B., Sokoloff, P., Stark, H., Goldberg, S.R. Dopamine D3 receptor hgands block nicotine-induced conditioned place preferences through a mechanism that does not involve discriminative-stimulus or antidepressant-like effects. Neuropsychopharmacology. 30 720, 2005. 

Figure 5.1 Visualization of the distribution of the DA transporter, D3 receptor, and K2-opioid receptor in the human brain of a drug-free control subject and a representative cocaine overdose victim. (A, B) The DA transporter was measured using [3H]WIN 35,428 (2 nM) as described previously. (C, D) The D3 receptor was measured using [3H]-(+)-7-OH-DPAT (1 nM) in the presence of GTP (300 m/W) to enhance the selective labeling of the D3 receptor subtype over the D2 receptor subtype as described previously. (E, F) The K2-opioid receptor subtype was measured using [125l]IOXY on tissue sections pretreated with BIT and FIT to occlude binding to the p- and 8-opioid receptors, respectively.

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