In vitro characterization of SLV308 (7‐[4‐methyl‐1‐piperazinyl]‐2(3H)‐benzoxazolone, monohydrochloride): A novel partial dopamine D2 and D3 receptor agonist and serotonin 5‐HT1A receptor agonist

  title={In vitro characterization of SLV308 (7‐[4‐methyl‐1‐piperazinyl]‐2(3H)‐benzoxazolone, monohydrochloride): A novel partial dopamine D2 and D3 receptor agonist and serotonin 5‐HT1A receptor agonist},
  author={Jeffrey C. Glennon and Guus van Scharrenburg and Eric Ronken and Mayke B. Hesselink and Jan Hendrik Reinders and Martina A W van der Neut and Stephen K. Long and Rolf W. Feenstra and Andrew C McCreary},
Present Parkinson's disease treatment strategies are far from ideal for a variety of reasons; it has therefore been suggested that partial dopamine receptor agonism might be a potential therapeutic approach with potentially fewer side effects. In the present study, we describe the in vitro characterization of the nonergot ligand SLV308 (7‐[4‐methyl‐1‐piperazinyl]‐2(3H)‐benzoxazolonemonohydrochloride). SLV308 binds to dopamine D2, D3, and D4 receptors and 5‐HT1A receptors and is a partial… 
Multitarget 1,4-Dioxane Compounds Combining Favorable D2-like and 5-HT1A Receptor Interactions with Potential for the Treatment of Parkinson's Disease or Schizophrenia.
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Synthesis and Biological Evaluation of a Series of Novel 1-(3-((6-Fluoropyridin-3-yl)oxy)propyl)piperazines as Dopamine/Serotonin Receptor Agonists
Twenty novel 1-(3-((6-fluoropyridin-3-yl)oxy)propyl)piperazine derivatives were designed and synthesized using a bioisosterism approach, and the results showed that several compounds exhibited a multitarget combination of D2/5-HT1A agonism.
Identification of N-propylnoraporphin-11-yl 5-(1,2-dithiolan-3-yl)pentanoate as a new anti-Parkinson's agent possessing a dopamine D2 and serotonin 5-HT1A dual-agonist profile.
Results suggest that 5-HT(1A) and D(2) dual-receptor agonist (-)-15 may present a novel candidate drug in the treatment of PD and LID.
Synthesis, Pharmacological Characterization and QSAR Modelling of 4-Phenylpiperidines and 4-Phenylpiperazines Effects on the dopaminergic neurotransmission in vivo
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Pardoprunox reverses motor deficits but induces only mild dyskinesia in MPTP‐treated common marmosets
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The Serotonin1A Receptor Partial Agonist S15535 [4-(Benzodioxan-5-yl)1-(indan-2-yl)piperazine] Enhances Cholinergic Transmission and Cognitive Function in Rodents: A Combined Neurochemical and Behavioral Analysis
S15535 reinforces frontocortical and hippocampal release of acetylcholine and displays a broad-based pattern of procognitive properties, which are consistent with previous work on cholinergic transmission and cognitive function in rodents.
S33084, a novel, potent, selective, and competitive antagonist at dopamine D(3)-receptors: I. Receptorial, electrophysiological and neurochemical profile compared with GR218,231 and L741,626.
S33084 is a novel, potent, selective, and competitive antagonist at hD(3)-receptors that tonically inhibit ascending dopaminergic pathways, although the latter may contribute to phasic suppression of DA release in frontal cortex.
Differential activation of Gq/11 and Gi(3) proteins at 5-hydroxytryptamine(2C) receptors revealed by antibody capture assays: influence of receptor reserve and relationship to agonist-directed trafficking.
H5-HT(2C) receptors couple to both Gq/11 and Gi(3) in CHO cells, and efficacy for G protein subtype activation is both ligand- and receptor reserve-dependent, as determined by a guanosine 5'-O-(3-[(35)S]GTPgammaS]thio)triphosphate binding assay.
Pharmacological actions of a novel, high-affinity, and selective human dopamine D(3) receptor antagonist, SB-277011-A.
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Motor effects of the partial dopamine agonist (−)‐3‐(3‐hydroxyphenyl)‐N‐n‐propylpiperidine (preclamol) in Parkinson's disease
  • L. Metman, V. Sethy, T. Chase
  • Psychology, Medicine
    Movement disorders : official journal of the Movement Disorder Society
  • 1994
The results suggest that partial dopamine agonists can exert agonist or antagonist activity in parkinsonian patients depending on concurrent dopaminergic tone and that this class of agents may have relatively limited clinical utility.
G protein activation by human dopamine D3 receptors in high-expressing Chinese hamster ovary cells: A guanosine-5'-O-(3-[35S]thio)- triphosphate binding and antibody study.
The data suggest that hD3 receptors may couple to Galphaq/alpha11 and would be consistent with the observation that pertussis toxin pretreatment, which inactivates only Gi/o proteins, only submaximally blocked dopamine-stimulated [35S]GTPgammaS binding in CHO-hD3 cells.
Aripiprazole, a Novel Antipsychotic, Is a High-Affinity Partial Agonist at Human Dopamine D2 Receptors
These results, together with previous studies demonstrating partial agonist activity at serotonin 5-hydroxytryptamine (5-HT)1A receptors and antagonist activity at 5-HT2A receptors, support the identification of aripiprazole as a dopamine-serotonin system stabilizer.
Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile
Sarizotan at higher doses decreased DA precursor accumulation in reserpinized rats and induced contralateral rotational behavior in unilaterally substantia nigra lesioned rats, indicating some intrinsic dopaminergic activity.
Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. II. Agonist and Antagonist Properties at Subtypes of Dopamine D2-Like Receptor and α1/α2-Adrenoceptor
In conclusion, antiparkinson agents display diverse agonist and antagonist properties at multiple subtypes of D2-like receptor and α1/α2-AR, actions, which likely contribute to their contrasting functional profiles.