Disease relevance of DRD2

• The effects of quinpirole, a specific dopamine D2 receptor agonist, were investigated on cardiovascular responses and plasma levels of catecholamines and vasopressin in two groups of conscious dogs: (1) control dogs and (2) dogs with diabetes insipidus (i.e. animals surgically deprived of vasopressin) [1].
• The emesis induced by cisplatin (3 mg/kg, i.v.) was inhibited by the intravenous administration of ICS205930 (2 x 0.01 or 2 x 0.1 mg/kg) and MDL72222 (2 x 0.5 mg/kg), 5-HT3 receptor antagonists, but not by the intravenous administration of metoclopramide (2 x 0.5 mg/kg), a dopamine D2 receptor antagonist [2].

High impact information on DRD2

• Synthesis and structure-affinity relationships of novel N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)pyridine-3-carboxamides with potent serotonin 5-HT3 and dopamine D2 receptor antagonistic activity [3].
• Since quinpirole has a reported Ki value of 5.1 nM for dopamine D3 receptors, similar to the quinpirole Ki value of 4.8 nM for the high-affinity state of the dopamine D2 receptor, it appears that [3H]quinpirole with its Kd of 3.9-6.8 nM could label both these two dopamine receptors [4].
• The present study demonstrates that the decrease in blood pressure elicited by quinpirole is associated with an increase in vasopressin release, which counteracts the hypotensive effect of the the dopamine D2 receptor agonist [1].
• This study evaluated the coronary dopamine receptors by using the dopamine D1 receptor agonist fenoldopam, dopamine D2 receptor agonist propylbutyldopamine, and their selective antagonists SCH23390 and domperidone [5].
• A dopamine D2 receptor photolabel: azidoclebopride [6].

Biological context of DRD2

• Beagle bitches were administered the dopamine D2 receptor agonist cabergoline in 3 groups of 5 animals each, starting on known days of the estrous cycle [7].

Anatomical context of DRD2

• The same effect, but weaker, was obtained using bilateral microinjections of the dopamine D2 receptor blocker raclopride into the neostriatum [8].

Associations of DRD2 with chemical compounds

• Effects of dopamine D1 and dopamine D2 receptor agonists on coronary and peripheral hemodynamics [5].
• Among the compounds, 5-chloro-N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)-2-methoxy-4-methylaminobenzamide (82), 5-bromo (110), and 5-iodo (112) analogues exhibited a much higher affinity for the dopamine D2 receptor than that of metoclopramide (IC50=17.5-61.0 nM vs. 483 nM) [9].
• In behavioral studies, haloperidol (a dopamine D2 receptor antagonist) prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake blocker) has the cross-behavioral sensitization with MAP [10].
• Dopamine D2 receptor binding subunits of the porcine anterior pituitary were visualized by autoradiography following photoaffinity labeling with [125I]N-azidophenethylspiperone and sodium dodecyl-sulfate polyacrylamide gel electrophoresis [11].
• Introduction of one methyl group on the nitrogen atom at the 4-position and/or modification of the substituent at the 5-position of the 4-amino-5-chloro-2-methoxybenzoyl moiety caused a marked increase in the dopamine D2 receptor binding affinity along with a potent 5-HT3 receptor binding affinity [9].

Analytical, diagnostic and therapeutic context of DRD2

• From the results of both in vitro receptor binding and in vivo biological assays for the dopamine D2 receptor, 1-ethyl-4-methylhexahydro-1,4-diazepine ring was selected as an optimum amine moiety [9].
• The radioligand 18F-2 holds promise for positron emission tomography studies of the dopamine D-2 receptor system based upon its selective, potent binding and resistance to displacement by endogenous dopamine [12].

References