Genetic variation and dopamine D2 receptor availability: a systematic review and meta-analysis of human in vivo molecular imaging studies

Compound D2AAK1_3 was designed as a modification of the lead structure D2AAK1 (an in vivo active multi-target compound with nanomolar affinity to a number of aminergic GPCRs) and synthesized in the reaction of 5-ethoxyindole and 1-benzyl-4-piperidone. This compound has an affinity to the human dopamine D2 receptor with Ki of 151 nM. The aim of these studies was the structural and thermal characterization of the compound D2AAK1_3. In particular; X-ray studies; molecular docking and molecular dynamics as well as thermal analysis were performed. The studied compound crystallizes in orthorhombic system; in chiral space group P212121. The compound has a non-planar conformation. The studied compound was docked to the novel X-ray structure of the human dopamine D2 receptor in the inactive state (PDB ID: 6CM4) and established the main contact between its protonatable nitrogen atom and Asp (3.32) of the receptor. The obtained binding pose was stable in molecular dynamics simulations. Thermal stability of the compound was investigated using the TG-DSC technique in the air atmosphere, while TG-FTIR analyses in air and nitrogen atmospheres were also performed. The studied compound is characterized by good thermal stability. The main volatile products of combustion are the following gases: CO2; H2O toluene and CO while in the case of pyrolysis process in the FTIR spectra; the characteristic bands of NH3; piperidine and indole are additionally observed.

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CORRECTION TO “COMPARISON OF PREDICTION METHODS FOR IN VIVO CLEARANCE OF (S,S)-3-[3-(METHYLSULFONYL)PHENYL]-1-PROPYLPIPERIDINE HYDROCHLORIDE, A DOPAMINE D2 RECEPTOR ANTAGONIST, IN HUMANS”

Drug Metabolism and Disposition ◽

10.1124/dmd.32.10.1199 ◽

2004 ◽

Vol 32 (10) ◽

pp. 1199-1199

Keyword(s):

Receptor Antagonist ◽

Dopamine D2 Receptor ◽

D2 Receptor ◽

Prediction Methods ◽

Dopamine D2 ◽

Dopamine D2 Receptor Antagonist

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Antipsychotics, dopamine D2 receptor occupancy and clinical improvement in schizophrenia: A meta-analysis

Schizophrenia Research ◽

10.1016/j.schres.2012.06.027 ◽

2012 ◽

Vol 140 (1-3) ◽

pp. 214-220 ◽

Cited By ~ 29

Author(s):

Zeynep Yilmaz ◽

Clement C. Zai ◽

Rudi Hwang ◽

Steve Mann ◽

Tamara Arenovich ◽

...

Keyword(s):

Clinical Improvement ◽

Dopamine D2 Receptor ◽

Meta Analysis ◽

D2 Receptor ◽

Receptor Occupancy ◽

Dopamine D2 ◽

Dopamine D2 Receptor Occupancy

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Dopamine D2 Receptor Blockade and Antimigraine Action of Flunarizine

Cephalalgia ◽

10.1046/j.1468-2982.1994.014003235.x ◽

1994 ◽

Vol 14 (3) ◽

pp. 235-240 ◽

Cited By ~ 14

Author(s):

C Wöber ◽

T Brücke ◽

C Wöber-Bingöl ◽

S Asenbaum ◽

P Wessely ◽

...

Keyword(s):

Single Photon ◽

Dopamine D2 Receptor ◽

Photon Emission ◽

D2 Receptor ◽

High Specificity ◽

D2 Receptors ◽

Binding Potential ◽

Receptor Blockade ◽

Dopamine D2

We studied in vivo the influence of flunarizine on dopamine D2 receptors and investigated whether dopamine D2 receptor blockade is involved in its antimigraine action. Eleven migraine patients, treated with flunarizine, 10 mg per day, underwent single photon emission computer tomography (SPECT) using [123I] labeled iodobenzamide, a ligand with high affinity and high specificity for D2 receptors. There was a reduction of the dopamine D2 receptor binding potential in all patients compared to age-matched controls. The efficacy of flunarizine in migraine prophylaxis failed to correlate with the degree of the dopamine D2 receptor blockade. The antimigraine action of flunarizine may not involve antidopaminergic mechanisms.

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