Selective dopamine D3 receptor antagonists enhance cortical acetylcholine levels measured with high-performance liquid chromatography/tandem mass spectrometry without anti-cholinesterases

Lacroix, Laurent; Ceolin, Laura; Zocchi, Alessandro; Varnier, Giorgia; Garzotti, Marco; Curcuruto, Ornella; Heidbreder, Christian

doi:10.1016/j.jneumeth.2006.03.017

Cited by 52 publications

(44 citation statements)

References 32 publications

(39 reference statements)

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“…The above findings coincide with evidence that preferential blockade of D 3 versus D 2 receptors preserves and even enhances cognitive performance (Laszy et al, 2005;Micale et al, 2006;Millan et al, 2007). Cholinergic pathways in the FCX, subject to tonic inhibition by D 3 receptors, are a potential substrate for this beneficial influence of D 3 antagonists upon cognition (Sarter et al, 2005;Lacroix et al, 2006;Millan et al, 2007). Accordingly, S33138 elevated extracellular levels of ACh in FCX at low doses similar to those active in the social recognition procedure and other models of D 3 receptor-mediated activity (Millan et al, 2008b).…”

Section: Elevation By S33138 Of Extracellular Levels Of Histamine Butsupporting

confidence: 77%

“…Furthermore, we determined its effects in a model of "aversive learning," the passive avoidance (PAV) paradigm in rats (Hagan and Jones, 2005;El-Ghundi et al, 2007). Inasmuch as D 3 receptor blockade enhances frontocortical release of acetylcholine (ACh) (Lacroix et al, 2006;Millan et al, 2007), the influence of S33138 upon extracellular levels of ACh was determined in the FCX of freely moving rats. Moreover, we examined its influence upon levels of histamine, monoamines, glutamate, and GABA, neurotransmitters likewise implicated in the control of cognition and perturbed in schizophrenia (Bacciottini et al, 2001;Ito, 2004;Millan, 2005;Lewis and Gonzalez-Burgos, 2006;Tanaka, 2006).…”

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confidence: 99%

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S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), a Preferential Dopamine D₃ versus D₂ Receptor Antagonist and Potential Antipsychotic Agent: III. Actions in Models of Therapeutic Activity and Induction of Side Effects

Millan¹,

Loiseau²,

Dekeyne³

et al. 2007

J Pharmacol Exp Ther

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In contrast to clinically available antipsychotics, the novel benzopyranopyrrolidine derivative, S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1]benzopyrano [3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), behaves as a preferential antagonist of D 3 versus D 2 receptors and does not interact with histamine H 1 and muscarinic receptors. In contrast to haloperidol, clozapine, olanzapine, and risperidone, S33138 (0.16 -2.5 mg/kg s.c.) did not disrupt performance in passive-avoidance and five-choice serial reaction time procedures. Furthermore, upon either systemic administration (0.04 -2.5 mg/kg s.c.) or introduction into the frontal cortex (0.04 -0.63 g/side), S33138 potently attenuated the perturbation of social recognition by scopolamine or a prolonged intersession delay. Over a comparable and low-dose range, S33138 (0.04 -0.63 mg/kg s.c.) elevated dialysis levels of acetylcholine in the frontal cortex of freely moving rats. At higher doses (2.5-10.0 mg/kg s.c.), S33138 also increased frontocortical levels of histamine, whereas monoamines, glutamate, glycine, and GABA were unaffected. By analogy to the other antipsychotics, S33138 (0.63-10.0 mg/kg s.c.) inhibited conditioned avoidance responses in rats, apomorphine-induced climbing in mice, and hyperlocomotion elicited by amphetamine, cocaine, dizocilpine, ketamine, and phencyclidine in rats. S33138 (0.16 -2.5 mg/kg s.c.) also blocked the reduction of prepulse inhibition elicited by apomorphine. In comparison with the above actions, only "high" doses of S33138 (10.0 -40.0 mg/kg s.c.) elicited catalepsy. To summarize, reflecting preferential blockade of D 3 versus D 2 receptors, S33138 preserves and/or enhances cognitive function, increases frontocortical cholinergic transmission, and is active in models of antipsychotic properties at doses well below those inducing catalepsy. In comparison with clinically available agents, S33138 displays, thus, a distinctive and promising profile of potential antipsychotic properties.We have recently described a novel benzopyranopyrrolidine derivative, S33138 (Millan et al., 2008a,b) that behaves as a preferential antagonist at cloned, human, and native cerebral dopaminergic D 3 versus D 2 receptors. In addition, it displays modest antagonist properties at serotonin (5-HT) 2A receptors, 5-HT 7 receptors, and ␣ 2C -adrenoceptors (ARs), blockade of which may also be useful in the treatment of schizophrenia Svensson, 2003). In contrast, S33138 does not interact with histamine H 1 , muscarinic, or ␣ 1 -adrenoceptors, antagonism of which provokes cardiovascular-autonomic side effects (Kroeze et al., 2003;Lieberman, 2005). This distinctive receptor-binding profile differentiates S33138 from clinically employed antipsychotics like the neuroleptic and D 2 /D 3 receptor antagonist, haloperidol; the "atypical" agent, clozapine; and two further mulArticle, publication date, and citation information can be found at

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Section: Elevation By S33138 Of Extracellular Levels Of Histamine Butsupporting

confidence: 77%

mentioning

confidence: 99%

S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), a Preferential Dopamine D₃ versus D₂ Receptor Antagonist and Potential Antipsychotic Agent: III. Actions in Models of Therapeutic Activity and Induction of Side Effects

Millan¹,

Loiseau²,

Dekeyne³

et al. 2007

J Pharmacol Exp Ther

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“…The molecular ion (M + ) at m/z 146 of ACh is the predominant ion formed in the ESI source at a low pH of the mobile phase. The limit of detection for ACh with LC-ESI-MS/MS is in the range of 0.2-1.4 fmol (Hows et al, 2002;Lacroix et al, 2006;Shackman et al, 2007;Uutela et al, 2005;Zhu et al, 2000), indicating better sensitivity than with LC-ECD. In addition, the multiple reaction monitoring (MRM) scan mode on a triple quadrupole mass spectrometer monitors specifi c daughter ions from dissociation of parent molecular ions.…”

Section: Mass Spectrometrymentioning

confidence: 97%

Quantification of acetylcholine, an essential neurotransmitter, in brain microdialysis samples by liquid chromatography mass spectrometry

Nirogi

Mudigonda

Kandikere

et al. 2009

Biomedical Chromatography

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Chemical neurotransmission has been the subject of intensive investigations in recent years. Acetylcholine is an essential neurotransmitter in the central nervous system as it has an effect on alertness, memory and learning. Enzymatic hydrolysis of acetylcholine in the synaptic cleft is fast and quickly metabolizes to choline and acetate by acetylcholinesterase. Hence the concentration in the extracellular fluid of the brain is low (0.1-6 nm). Techniques such as microdialysis are routinely employed to measure acetylcholine levels in living brain systems and the microdialysis sample volumes are usually less than 50 microL. In order to develop medicine for the diseases associated with cognitive dysfunction like mild cognitive impairment, Alzheimer's disease, schizophrenia and Parkinson's disease, or to study the mechanism of the illness, it is important to measure the concentration of acetylcholine in the extracellular fluid of the brain. Recently considerable attention has been focused on the development of chromatographic-mass spectrometric techniques to provide more sensitive and accurate quantification of acetylcholine collected from in-vivo brain microdialysis experiments. This review will provide a brief overview of acetylcholine biosynthesis, microdialysis technique and liquid chromatography mass spectrometry, which is being used to quantitate extracellular levels of acetylcholine.

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“…ACh has been detected by various methods, such as liquid chromatography/electrochemical (LC-EC) method [36][37][38], liquid chromatography/electrospray ionization/ mass spectrometry (LC-ESI-MS) [8,[39][40][41][42], liquid chromatography/atmospheric pressure chemical ionization/mass spectrometry (LC-APCI-MS) [43], as well as MALDI-TOF-MS with CHCA as the matrix [12]. The performances of these methods have been listed in detail on Table 3.…”

Section: Quantitative Methods Validation and Calibration Curvesmentioning

confidence: 99%

High Throughput Enzyme Inhibitor Screening by Functionalized Magnetic Carbonaceous Microspheres and Graphene Oxide-Based MALDI-TOF-MS

Liu

et al. 2011

J. Am. Soc. Mass Spectrom.

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In this work, a high throughput methodology for screening enzyme inhibitors has been demonstrated by combining enzyme immobilized magnetic carbonaceous microspheres and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with grapheme oxide as matrix. First, model enzyme acetylcholinesterase (AChE) was immobilized onto the 3-glycidoxypropyltrimethoxysilane (GLYMO)-modified magnetic carbonaceous (MC) microspheres, displaying a high enzyme activity and stability, and also facilitating the separation of enzyme from substrate and product. The efficiency of immobilized AChE was monitored by biochemical assay, which was carried out by mixing enzyme-immobilized MC microspheres with model substrate acetylcholine (ACh), and subsequent quantitative determination of substrate ACh and product choline using graphene oxide-based MALDI-TOF-MS with no background inference. The limit of detection (LOD) for ACh was 0.25 fmol/μL, and excellent linearity (R 2 =0.9998) was maintained over the range of 0.5 and 250 fmol/μL. Choline was quantified over the range of 0.05 and 15 pmol/μL, also with excellent linearity (R 2 =0.9994) and low LOD (0.15 fmol/μL). Good accuracy and precision were obtained for all concentrations within the range of the standard curves. All together, eight compounds (four known AChE inhibitors and four control chemical compounds with no AChE inhibit effect) were tested with our promoted methodology, and the obtained results demonstrated that our high throughput screening methodology could be a great help to the routine enzyme inhibitor screening.

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Selective dopamine D3 receptor antagonists enhance cortical acetylcholine levels measured with high-performance liquid chromatography/tandem mass spectrometry without anti-cholinesterases

Cited by 52 publications

References 32 publications

S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), a Preferential Dopamine D₃ versus D₂ Receptor Antagonist and Potential Antipsychotic Agent: III. Actions in Models of Therapeutic Activity and Induction of Side Effects

S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), a Preferential Dopamine D₃ versus D₂ Receptor Antagonist and Potential Antipsychotic Agent: III. Actions in Models of Therapeutic Activity and Induction of Side Effects

Quantification of acetylcholine, an essential neurotransmitter, in brain microdialysis samples by liquid chromatography mass spectrometry

High Throughput Enzyme Inhibitor Screening by Functionalized Magnetic Carbonaceous Microspheres and Graphene Oxide-Based MALDI-TOF-MS

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Selective dopamine D3 receptor antagonists enhance cortical acetylcholine levels measured with high-performance liquid chromatography/tandem mass spectrometry without anti-cholinesterases

Cited by 52 publications

References 32 publications

S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), a Preferential Dopamine D3 versus D2 Receptor Antagonist and Potential Antipsychotic Agent: III. Actions in Models of Therapeutic Activity and Induction of Side Effects

S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), a Preferential Dopamine D3 versus D2 Receptor Antagonist and Potential Antipsychotic Agent: III. Actions in Models of Therapeutic Activity and Induction of Side Effects

Quantification of acetylcholine, an essential neurotransmitter, in brain microdialysis samples by liquid chromatography mass spectrometry

High Throughput Enzyme Inhibitor Screening by Functionalized Magnetic Carbonaceous Microspheres and Graphene Oxide-Based MALDI-TOF-MS

Contact Info

Product

Resources

About

S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), a Preferential Dopamine D₃ versus D₂ Receptor Antagonist and Potential Antipsychotic Agent: III. Actions in Models of Therapeutic Activity and Induction of Side Effects

S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), a Preferential Dopamine D₃ versus D₂ Receptor Antagonist and Potential Antipsychotic Agent: III. Actions in Models of Therapeutic Activity and Induction of Side Effects