Dopamine is a biologically active amine synthesized in the central and peripheral nervous system. This biogenic monoamine acts by activating five types of dopamine receptors (D1-5 Rs), which belong to the G protein-coupled receptor family. Antagonists and partial agonists of D2 Rs are used to treat schizophrenia, Parkinson's disease, depression, and anxiety. The typical pharmacophore with high D2 R affinity comprises four main areas, namely aromatic moiety, cyclic amine, central linker and aromatic/heteroaromatic lipophilic fragment. From the literature reviewed herein, we can conclude that 4-(2,3-dichlorophenyl), 4-(2-methoxyphenyl)-, 4-(benzo[b]thiophen-4-yl)-1-substituted piperazine, and 4-(6-fluorobenzo[d]isoxazol-3-yl)piperidine moieties are critical for high D2 R affinity. Four to six atoms chains are optimal for D2 R affinity with 4-butoxyl as the most pronounced one. The bicyclic aromatic/heteroaromatic systems are most frequently occurring as lipophilic appendages to retain high D2 R affinity. In this review, we provide a thorough overview of the therapeutic potential of D2 R modulators in the treatment of the aforementioned disorders. In addition, this review summarizes current knowledge about these diseases, with a focus on the dopaminergic pathway underlying these pathologies. Major attention is paid to the structure, function, and pharmacology of novel D2 R ligands, which have been developed in the last decade (2010-2021), and belong to the 1,4-disubstituted aromatic cyclic amine group. Due to the abundance of data, allosteric D2 R ligands and D2 R modulators from patents are not discussed in this review.

• Klíčová slova
• D2 receptor agonist, D2 receptor antagonist, D2 receptor modulators, D2 receptor partial agonist, Parkinson's disease, anxiety, depression, dopamine, dopamine D2 receptor, schizophrenia,
• MeSH
• dopamin * metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• receptory dopaminu D2 * agonisté   metabolismus   MeSH
• receptory spřažené s G-proteiny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• dopamin * MeSH
• ligandy MeSH
• receptory dopaminu D2 * MeSH
• receptory spřažené s G-proteiny MeSH

AIMS: Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it increases expression of type 1 IP3 receptors (IP3R1). However, precise mechanism of haloperidol action on cardiomyocytes through dopaminergic signaling was not described yet. This study investigated a role of dopamine receptors in haloperidol-induced increase in IP3R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats. MATERIALS AND METHODS: We used differentiated NG-108 cells and H9c2 cells. Gene expression, Western blot and immunofluorescence were used to evaluate haloperidol-induced differences; proximity ligation assay (PLA) and immunoprecipitation to determine interactions of D1/D2 receptors. To evaluate cardiac parameters, Wistar albino male rats were used. KEY FINDINGS: We have shown that antagonism of D2R with either haloperidol or melperone results in upregulation of both, IP3R1 and Sig1R, which is associated with increased D2R, but reduced D1R expression. Immunofluorescence, immunoprecipitation and PLA support formation of heteromeric D1/D2 complexes in H9c2 cells. Treatment with haloperidol (but not melperone) caused decrease in systolic and diastolic blood pressure and significant increase in heart rate. SIGNIFICANCE: Because D1R/D2R complexes can engage Gq-like signaling in other experimental systems, these results are consistent with the possibility that disruption of D1R/D2R complex in H9c2 cells might cause a decrease in IP3R1 activity, which in turn may account for the increase expression of IP3R and Sig1R. D2R is probably not responsible for changes in cardiac parameters, since melperone did not have any effect.

• Klíčová slova
• D1R/D2R heterodimeric complex, Dopamine D2 receptor, H9c2 cell line, Haloperidol,
• MeSH
• antagonisté dopaminu D2 farmakologie   MeSH
• antagonisté dopaminu farmakologie   MeSH
• buněčné linie MeSH
• haloperidol farmakologie   MeSH
• potkani Wistar MeSH
• receptory dopaminu D1 genetika   metabolismus   MeSH
• receptory dopaminu D2 genetika   metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• srdce účinky léků   MeSH
• srdeční frekvence účinky léků   MeSH
• vazba proteinů účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antagonisté dopaminu D2 MeSH
• antagonisté dopaminu MeSH
• haloperidol MeSH
• receptory dopaminu D1 MeSH
• receptory dopaminu D2 MeSH

The possible involvement of dopamine D1 receptors in the regulation of acetylcholine release in the rabbit caudate nucleus was investigated. Caudate slices, preincubated with [3H]choline, were superfused continuously and subjected to electrical field stimulation with only a single pulse. In agreement with the view that the release of acetylcholine evoked by a single electrical pulse is not influenced by endogenous transmitters, atropine and domperidone failed to increase the evoked release of [3H]acetylcholine, whereas oxotremorine and quinpirole caused a concentration-dependent inhibition of transmitter release. Neither the dopamine D1 receptor antagonist SCH 23390 nor the D1 agonist SKF 38393 in a concentration range of 0.01-1 mumol/l changed the evoked [3H]acetylcholine release. The inhibitory effect of the dopamine D2 receptor agonist quinpirole was virtually abolished in the presence of 0.1 mumol/l domperidone and diminished in the presence of 1 mumol/l SCH 23390. It remained unchanged in the presence of 1 mumol/l SKF 38393. It is concluded that the inhibition of acetylcholine release by dopamine is mediated exclusively via presynaptic dopamine D2 receptors and that the antagonistic effect of SCH 23390 on the inhibition of acetylcholine release by quinpirole is due to its interaction with dopamine D2 rather than D1 receptors located on cholinergic nerve terminals.

• MeSH
• acetylcholin metabolismus   MeSH
• corpus striatum účinky léků   metabolismus   MeSH
• dopamin farmakologie   MeSH
• dopaminové látky farmakologie   MeSH
• elektrická stimulace MeSH
• elektrofyziologie MeSH
• králíci MeSH
• receptory dopaminové fyziologie   MeSH
• receptory dopaminu D1 MeSH
• receptory dopaminu D2 MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcholin MeSH
• dopamin MeSH
• dopaminové látky MeSH
• receptory dopaminové MeSH
• receptory dopaminu D1 MeSH
• receptory dopaminu D2 MeSH

Spatial navigation attracts the attention of neuroscientists as an animal analogue of human declarative memory. The Carousel maze is a dry-land navigational paradigm, which proved to be useful in studying neurobiological substrates of learning. The task involves avoidance of a stable sector on a rotating arena and is highly dependent upon the hippocampus. The present study aims at testing hypothesis that sulpiride (a centrally-active dopamine D2-like receptor antagonist) and propranolol (a beta-blocker) impair spatial learning in the Carousel maze after combined systemic administration. These doses were previously shown to be subthreshold in this task. Results showed that both substances affected behavior and significantly potentiated their negative effects on spatial learning. This suggests central interaction of both types of receptors in influencing acquisition of this dynamic-environment task.

• MeSH
• antagonisté dopaminu D2 * MeSH
• antagonisté dopaminu aplikace a dávkování   MeSH
• beta blokátory aplikace a dávkování   MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• potkani Long-Evans MeSH
• propranolol aplikace a dávkování   MeSH
• prostorové chování účinky léků   fyziologie   MeSH
• psychomotorický výkon účinky léků   fyziologie   MeSH
• receptory dopaminu D2 fyziologie   MeSH
• sulpirid aplikace a dávkování   MeSH
• synergismus léků MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antagonisté dopaminu D2 * MeSH
• antagonisté dopaminu MeSH
• beta blokátory MeSH
• propranolol MeSH
• receptory dopaminu D2 MeSH
• sulpirid MeSH

In this pilot study, a series of new 3,4-dihydroquinolin-2(1H)-one derivatives as potential dopamine receptor D2 (D2R) modulators were synthesized and evaluated in vitro. The preliminary structure-activity relationship disclosed that compound 5e exhibited the highest D2R affinity among the newly synthesized compounds. In addition, 5e showed a very low cytotoxic profile and a high probability to cross the blood-brain barrier, which is important considering the observed affinity. However, molecular modelling simulation revealed completely different binding mode of 5e compared to USC-D301, which might be the culprit of the reduced affinity of 5e toward D2R in comparison with USC-D301.

• Klíčová slova
• aripiprazole, blood–brain barrier, dopamine receptor, molecular modeling studies, schizophrenia,
• MeSH
• aripiprazol chemická syntéza   farmakologie   MeSH
• buněčná smrt MeSH
• centrální nervový systém účinky léků   MeSH
• chinolony chemická syntéza   chemie   farmakologie   MeSH
• CHO buňky MeSH
• Cricetulus MeSH
• hematoencefalická bariéra účinky léků   patologie   MeSH
• ligandy MeSH
• molekulární modely MeSH
• racionální návrh léčiv MeSH
• receptory dopaminu D2 chemie   metabolismus   MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aripiprazol MeSH
• chinolony MeSH
• dihydroquinolin-2(1H)-one MeSH Prohlížeč
• ligandy MeSH
• receptory dopaminu D2 MeSH

Dopaminergic neurotransmission is involved in several brain functions including spatial cognition. In the present study we examine the effects of systemic administration of D1-like receptor antagonist SCH23390 and D2-like receptor antagonist sulpiride on the acquisition of the Morris water maze task. We used visible versus hidden platform versions of the MWM in order to distinguish between the effects of the drugs on the procedural versus cognitive aspects of the task. SCH23390 was found to prolong escape latencies to the visible platform at a higher dose (0.05mg/kg), whilst the lower dose (0.02mg/kg) left both procedural and cognitive functions almost unchanged. SCH23390 was also found to reduce swimming speed. Sulpiride did not affect the visible platform learning at any of three doses studied (30, 60 and 100mg/kg); the highest dose of sulpiride (100mg/kg) impaired place navigation to the hidden platform, without affecting the swim speed. The results of the present study show a difference in the involvement of D1-like and D2-like receptors in the MWM acquisition.

• MeSH
• antagonisté dopaminu D2 * MeSH
• antagonisté dopaminu farmakologie   MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• chování zvířat účinky léků   MeSH
• krysa rodu Rattus MeSH
• potkani inbrední LEC MeSH
• receptory dopaminu D1 antagonisté a inhibitory   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antagonisté dopaminu D2 * MeSH
• antagonisté dopaminu MeSH
• receptory dopaminu D1 MeSH

PURPOSE: Spindle cell oncocytomas (SCOs) are very rare tumors of the posterior pituitary with potential for locally aggressive behaviour. Their treatment includes surgery and possibly radiotherapy, however other options are lacking. Somatostatin receptors (SSTs) are a possible therapeutic target for somatostatin analogues and their expression has been demonstrated recently in closely related pituicytomas, but there are no data about their presence in SCOs. METHODS: We collected five cases of SCO from four patients including one recurrent case. Immunohistochemical detection of TTF1, GFAP, CD68, SST1, SST2, SST3, SST5 and D2 dopamine receptor (D2DR) was performed. Intensity, percentage of positive cells and pattern of expression was evaluated in semiquantitative fashion. Protein expression of SST1-5 and D2DR was further evaluated by western blot. RESULTS: Mean patient age was 61.8 years (range 47-71 years) with male to female ratio 1:1. In one patient, samples from the original tumor and its recurrence 16 years later were assessed. TTF1 was positive in all five cases, no expression of GFAP and CD68 was seen. Immunohistochemical expression of SST1 was noted in 1/5 cases, SST2 in 2/5 cases, including recurrent case but not the original case. SST3 was expressed in 3/5 tumors and D2 dopamine receptor in 4/5 cases. Western blot was successfully performed in four samples. SST2, SST3 and D2DR expression was identified in all the samples, including two cases originally negative for SST2 and one case negative for SST3 by immunohistochemistry. The number of positive cells and level of expression varied among different areas of the same tumors. No expression of SST5 was observed. In the patient with the recurrent tumor, intensity of SST2, SST3 and D2DR expression varied between original tumor and its recurrence. CONCLUSIONS: We demonstrated presence of different SST subtypes and D2DR in spindle cell oncocytomas. The most commonly expressed subtype was SST2 and SST3, while no expression of SST5 was observed. Expression showed spatial heterogeneity and temporal changes as seen in the recurrent case. The biological meaning of SSTs expression in SCOs is unclear as well as whether it may be exploited in treatment of selected cases.

• Klíčová slova
• Posterior pituitary, Predictive markers, Somatostatin receptors, Spindle cell oncocytoma,
• MeSH
• akromegalie metabolismus   patologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci štítné žlázy metabolismus   patologie   MeSH
• oxyfilní adenom metabolismus   patologie   MeSH
• papilární karcinom štítné žlázy metabolismus   patologie   MeSH
• receptory dopaminu D2 metabolismus   MeSH
• receptory somatostatinu metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• receptory dopaminu D2 MeSH
• receptory somatostatinu MeSH
• somatostatin receptor 2 MeSH Prohlížeč
• somatostatin receptor 3 MeSH Prohlížeč
• somatostatin receptor 5 MeSH Prohlížeč
• somatostatin receptor type 1 MeSH Prohlížeč

The process of locomotion is controlled by fine-tuned dopaminergic neurons in the Substantia Nigra pars-compacta (SNpc) that projects their axons to the dorsal striatum regulating cortical innervations of medium spiny neurons. Dysfunction in dopaminergic neurotransmission within the striatum leads to movement impairments, gaiting defects, and hypo-locomotion. Due to their high polarity and extreme axonal arborization, neurons depend on molecular motor proteins and microtubule-based transport for their normal function. Transport defects have been associated with neurodegeneration since axonopathies, axonal clogging, microtubule destabilization, and lower motor proteins levels were described in the brain of patients with Parkinson's Disease and other neurodegenerative disorders. However, the contribution of specific motor proteins to the regulation of the nigrostriatal network remains unclear. Here, we generated different conditional knockout mice for the kinesin heavy chain 5B subunit (Kif5b) of Kinesin-1 to unravel its contribution to locomotion. Interestingly, mice with neuronal Kif5b deletion showed hypo-locomotion, movement initiation deficits, and coordination impairments. High pressure liquid chromatography determined that dopamine (DA) metabolism is impaired in neuronal Kif5b-KO, while no dopaminergic cell loss was observed. However, the deletion of Kif5b only in dopaminergic neurons is not sufficient to induce locomotor defects. Noteworthy, pharmacological stimulation of DA release together with agonist or antagonist of DA receptors revealed selective D2-dependent movement initiation defects in neuronal Kif5b-KO. Finally, subcellular fractionation from striatum showed that Kif5b deletion reduced the amount of dopamine D2 receptor in synaptic plasma membranes. Together, these results revealed an important role for Kif5b in the modulation of the striatal network that is relevant to the overall locomotor response. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

• Klíčová slova
• Kif5b, axonal transport, dopamine, dopamine receptors, locomotor response, nigrostriatal pathway,
• MeSH
• corpus striatum metabolismus   MeSH
• dopaminergní neurony metabolismus   MeSH
• kineziny metabolismus   MeSH
• lokomoce fyziologie   MeSH
• myši knockoutované MeSH
• myši MeSH
• receptory dopaminu D2 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Kif5b protein, mouse MeSH Prohlížeč
• kineziny MeSH
• receptory dopaminu D2 MeSH

The involvement of catecholamine receptors (alpha-adrenergic, D2-dopamine (DA)) was investigated in restraint stress influenced immune responses with concomitant changes of G-protein signal transduction. Impairment of the spleen morphology, TH1/TH2 cytokine network and natural killer (NK) cell function was observed. In vivo administration of specific antagonists prior to restraint stress reversed the immunosuppression. These findings demonstrate that D2-type dopaminergic mechanism represents the dominant component in regulation of Galphas/Galphai(1,2)/Galphaq/11-protein signal transduction and contribute to cell responses at postreceptor level of both, central nervous and immune systems. G-protein-coupled receptors (GPCRs) can modulate cytokine production and may play a regulatory role in immune effector mechanisms.

• MeSH
• alfa blokátory farmakologie   MeSH
• alfa-adrenergní receptory účinky léků   imunologie   MeSH
• antagonisté dopaminu D2 MeSH
• antagonisté dopaminu farmakologie   MeSH
• B-lymfocyty cytologie   imunologie   MeSH
• buňky NK cytologie   imunologie   MeSH
• fenotyp MeSH
• fyziologický stres imunologie   metabolismus   patofyziologie   MeSH
• imunitní systém účinky léků   imunologie   MeSH
• katecholaminy imunologie   MeSH
• leukocyty mononukleární cytologie   účinky léků   imunologie   MeSH
• mozek účinky léků   imunologie   metabolismus   MeSH
• myši inbrední CBA MeSH
• myši MeSH
• neuroimunomodulace účinky léků   imunologie   MeSH
• neurosekreční systémy účinky léků   imunologie   MeSH
• proteiny vázající GTP imunologie   MeSH
• receptory dopaminu D2 imunologie   MeSH
• slezina cytologie   účinky léků   imunologie   MeSH
• T-lymfocyty cytologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa blokátory MeSH
• alfa-adrenergní receptory MeSH
• antagonisté dopaminu D2 MeSH
• antagonisté dopaminu MeSH
• katecholaminy MeSH
• proteiny vázající GTP MeSH
• receptory dopaminu D2 MeSH

OBJECTIVES: In our previous studies we found that both acute administration of CB1 receptor agonist methanandamide and repeated methanandamide pre-treatment prior to methamphetamine challenge dose elicited increase in the CB1 receptor mRNA expression in the mouse mesencephalon. As a reciprocal cross-talk is reported between the cannabinoid CB1 and dopamine receptors, that are highly co-localized on brain neurones, we targeted possible changes in relative expression of dopamine D1 and D2 receptor mRNA in mesencephalon in mice sensitized by repeated treatments to methamphetamine stimulatory effects and cross-sensitized to methamphetamine by cannabinoid CB1 receptor agonist methanandamide pre-treatment. METHODS: To confirm development of behavioural sensitization or cross-sensitization, respectively, we observed changes in locomotion using the open field test. Mice were treated repeatedly with either methamphetamine or methamphetamine after repeated pre-treatment with methanandamide. After each measurement of locomotion one third of animals were sacrificed and the brain was stored. RNA was isolated from the midbrain and used for reverse transcription and subsequent real-time PCR. RESULTS AND CONCLUSION: As in many of our earlier studies with the same dosage regimen we found in the behavioural part both development of sensitization to methamphetamine stimulatory effects after repeated treatment and cross-sensitization to them by pre-treatment with cannabinoid receptor CB1 agonist methanandamide. Real-time PCR analyses showed an increase in D1 receptor mRNA expression after the first dose of methamphetamine (that persisted also after the last dose of methamphetamine) and after the first dose of methanandamide (which also persisted after the methamphetamine challenge dose). In opposite a significant decrease in D2 receptor mRNA expression both after the first dose of methamphetamine and methanandamide (that persisted also after the methamphetamine challenge doses) was registered. Thus, our results suggest that both methamphetmine and methanandamide treatment can provoke changes in dopamine receptor density in mouse mesenpcephalon, the increase in D1 and decrease in D2 receptor subtypes.

• MeSH
• chování zvířat účinky léků   MeSH
• dopaminové látky farmakologie   MeSH
• interakce mezi receptory a ligandy účinky léků   MeSH
• kyseliny arachidonové farmakologie   MeSH
• lékové interakce MeSH
• messenger RNA analýza   MeSH
• methamfetamin farmakologie   MeSH
• mezencefalon účinky léků   metabolismus   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• náhodné rozdělení MeSH
• pohybová aktivita účinky léků   MeSH
• receptor kanabinoidní CB1 agonisté   MeSH
• receptory dopaminu D1 účinky léků   genetika   metabolismus   MeSH
• receptory dopaminu D2 účinky léků   genetika   metabolismus   MeSH
• rozvrh dávkování léků MeSH
• senzibilizace centrálního nervového systému účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dopaminové látky MeSH
• kyseliny arachidonové MeSH
• messenger RNA MeSH
• methamfetamin MeSH
• methanandamide MeSH Prohlížeč
• receptor kanabinoidní CB1 MeSH
• receptory dopaminu D1 MeSH
• receptory dopaminu D2 MeSH