Search results for "Dopamine receptor"
showing 10 items of 125 documents
In vitro affinities of various halogenated benzamide derivatives as potential radioligands for non-invasive quantification of D(2)-like dopamine rece…
2007
Abstract Benzamide derivatives as radiotracers have played an important role in diagnosing malfunction in dopaminergic neurotransmission. A variety of halogenated and two unsubstituted benzamide derivatives were synthesised and their in vitro affinities to dopaminergic, serotonergic and adrenergic receptors and their lipophilicities were determined. As references IBZM (3), raclopride (4) and FLB457 (5) were tested as well. The two iodinated compounds NAE (27) and NADE (28) displayed Ki values of 0.68 and 14 nM for the D2 receptor. The well-established radiotracers FP (1) and DMFP (2) showed affinities in the same range as did the brominated compounds NABrE (29) and NABrDE (30). The log D7.4…
3,4-Dihydroxy- and 3,4-methylenedioxy- phenanthrene-type alkaloids with high selectivity for D2 dopamine receptor.
2013
Abstract Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new drugs acting at the dopamine receptors (DR) as potential new targets for the treatment of schizophrenia or Parkinson’s disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) can behave as selective D 2 dopaminergic alkaloids. In the present study we have synthesized five aporphine compounds and five phenanthrene alkaloids and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and…
Synthesis and Dopamine Receptor Selectivity of the Benzyltetrahydroisoquinoline, (R)-(+)-nor-Roefractine
1998
(R)-(+)-nor-Roefractine (1) was synthesized by the Bischler-Napieralski route, using asymmetric reduction of the 1, 2-didehydro precursor imine with sodium (S)-N-CBZ-prolinyloxyborohydride. Compound 1 was able to displace [3H]-raclopride (a D2 dopamine receptor-selective ligand) from its specific binding sites in rat striatum with selectivity vs [3H]-SCH23390 (D1 dopamine receptor-selective ligand).
Syntheses of dopaminergic 1-cyclohexylmethyl-7,8-dioxygenated tetrahydroisoquinolines by selective heterogeneous tandem hydrogenation
2002
Abstract We describe the preparation in a ‘one-pot’ sequence 1-cyclohexylmethyl 7,8-dioxygenated tetrahydroisoquinoline, substituted and unsubstituted in the C ring by application of the Photo–Fries transposition, followed by a tandem reduction–cyclization and further reduction. Indeed, we have accomplished for the first time regioselective hydrogenation of the benzylic ring of the tetrahydroisoquinoline systems. All 1-cyclohexylmethyl THIQ synthesized were able to displace D2 dopamine receptor from its specific binding site in rat striatal membranes, while the N-methylated derivatives showed also affinity for D1 dopamine receptors.
D2R striatopallidal neurons inhibit both locomotor and drug reward processes.
2009
The specific functions of dopamine D(2) receptor-positive (D(2)R) striatopallidal neurons remain poorly understood. Using a genetic mouse model, we found that ablation of D(2)R neurons in the entire striatum induced hyperlocomotion, whereas ablation in the ventral striatum increased amphetamine conditioned place preference. Thus D(2)R striatopallidal neurons limit both locomotion and, unexpectedly, drug reinforcement.
Molecular recognition and binding mechanism of N-alkyl-benzyltetrahydroisoquinolines to the D1 dopamine receptor. A computational approach
2003
Fil: Suvire, Fernando Daniel. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia; Argentina
Postnatal developmental changes in the dopaminergic signaling in mouse gut
2011
The presence of dopamine-containing neurons in the enteric nervous system has been described, but it is far to be clear their role in the modulation of gut motility. Moreover, ontogenetic studies shows that dopaminergic neurons are late-developing neurons, arising perinatally, but there are no informations if dopaminergic signaling may undergo to developmental changes after birth, as demonstrated for other signaling. Thus, using a pharmacological approach, we examined, in vitro, the role of dopaminergic neurons in the regulation of duodenal contractility in neonatal mice (≤48 h postnatal) compared to the adults. Transcripts for all dopaminergic receptors were detected in mouse duodenum at e…
A Reassessment of the Therapeutic Potential of a Dopamine Receptor 2 Agonist (D2-AG) in Endometriosis by Comparison against a Standardized Antiangiog…
2021
Dopamine receptor 2 agonists (D2-ags) have been shown to reduce the size of tumors by targeting aberrant angiogenesis in pathological tissue. Because of this, the use of a D2-ag was inferred for endometriosis treatment. When assayed in mouse models however, D2-ags have been shown to cause a shift of the immature vessels towards a more mature phenotype but not a significant reduction in the amount of vascularization and size of lesions. These has raised concerns on whether the antiangiogenic effects of these compounds confer a therapeutic value for endometriosis. In the belief that antiangiogenic effects of D2-ags in endometriosis were masked due to non-optimal timing of pharmacological inte…
Structure-activity relationship of dopaminergic halogenated 1-benzyl-tetrahydroisoquinoline derivatives
2009
Two series of halogenated 1-benzyl-7-chloro-6-hydroxy-tetrahydroisoquinolines were prepared to explore the influence of each series on the affinity for dopamine receptors. All the compounds displayed a high affinity for D(1)-like and/or D(2)-like dopamine receptors in striatal membranes, although they were unable to inhibit [(3)H]-dopamine uptake in striatal synaptosomes. The halogen placed on the benzylic ring in 1-benzyl-THIQs, compounds of the series 1, 2'-bromobenzyl derivatives with K(i) values into the nanomolar range, and the series 2, 2',4'-dichlorobenzyl-THIQ homologues, proves to be an important factor to modulate affinity at dopamine receptor. (C) 2009 Elsevier Masson SAS. All ri…
Determination of Drug Concentrations in Serum and Dopamine Receptor Occupancy in Brain for Optimal Antipsychotic Drug Therapy
2009
Evidence has been given that antipsychotic effects of dopamine receptor antagonists are associated with 60 and 80% striatal dopamine D2 and D3 receptor occupancy. Receptor occupancy correlates well with concentrations of the antipsychotic drugs in serum or plasma, much better than the dose. The latter is consistent with weak correlations between antipsychotic dose and serum concentrations and explained by the high interindividual variabilities in drug metabolism. Using positron emission tomography (PET) for in vivo determination of dopamine receptor occupancy in conjunction with drug concentration measurements “therapeutic windows” could be calculated for the atypical antipsychotic drugs am…