Effect of muscarinic receptor agonists xanomeline and sabcomeline on acetylcholine and dopamine efflux in the rat brain; comparison with effects of 4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one (AC260584) and N-desmethylclozapine

Li, Zhu; Snigdha, Shikha; Roseman, Alexander S.; Dai, Jin; Meltzer, Herbert Y.

doi:10.1016/j.ejphar.2008.08.009

Cited by 19 publications

(7 citation statements)

References 53 publications

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“… The average ACh levels (±SEM) in nM within the nucleus accumbens of rats. Basal value (Huang et al,2008; Ichikawa et al,2002a,c; Li et al,2008; Zangen and Hyodo,2002); NEO 0.3 μM (Keys and Mark,1998; Rada et al,2004,2006,2010); NEO 0.5 μM (Mark et al,1996; Parades et al,1999); NEO 1 μM (Del Arco et al,2007,2008); PHYS 5 μM (Consolo et al,1999); PHYS 10 μM (Lindefors et al,1992). …”

Section: Resultsmentioning

confidence: 99%

The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: A meta‐analysis

Noori

Fliegel

Brand

et al. 2012

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In vivo microdialysis has become a key method in investigating the dynamics of different neurotransmitter systems such as acetylcholine in the extracellular fluid. Depending on the sensitivity of the analytical method applied for measuring acetylcholine levels in brain dialysates, acetylcholinesterase (AChE) inhibitors are often used to increase the basal acetylcholine level up to a detectable magnitude. This artificial manipulation of the system questions the outcome of pharmacological studies and has led to a large number of experiments pursuing the appropriate physiological and pharmacological concentration of the AChE inhibitors in a range between 0.01 and 100 μM. However, the complexity of the action of these substances, particularly through the involvement of muscarinic autoreceptors and the induction of an autoinhibitory effect on acetylcholine release, did not allow this quest to be resolved completely and suggests the application of advanced mathematical methods for the evaluation of acetylcholine baseline levels. Here we performed a meta-analysis on published datasets of in vivo microdialysis measurements to assess the concentration-dependent effects of various AChE inhibitors on acetylcholine levels within the prefrontal cortex, nucleus accumbens, caudate putamen, and hippocampus in adult rats. In total 3255 rats were analyzed and we found that when compared with the minority of studies (14%) that did not use AChE inhibitors (these studies yielded basal levels between 0.55 and 2.71 nM depending on the brain site) an up to 350-fold increase in baseline values after the application of an inhibitor could be detected. Especially, the derivates neostigmine bromide and physostigmine sulfate seem to produce dramatic effects. Furthermore, concentration-dependent effects after the application of AChE inhibitors could not be established. In the case of neostigmine bromide an inverted concentration (0.1-10 μM)-response relationship was even detected. We conclude that although the presynaptic action of AChE inhibitors is well understood the nonphysiological and concentration-independent augmentation of the acetylcholine system requires the use of a standard protocol in order to produce replicable and comparable results. Our meta-analysis suggests the use of 0.1 μM neostigmine which produces an approximately 10-fold boost of brain baseline levels.

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Section: Resultsmentioning

confidence: 99%

The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: A meta‐analysis

Noori

Fliegel

Brand

et al. 2012

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“…; Li et al . ), and, thus, may contribute to the olanzapine‐ and lurasidone‐induced ACh release in the mPFC, since olanzapine has strong binding affinity for H 1 and muscarinic receptors, as does lurasidone for alpha 2 receptors (Ishibashi et al . , ).…”

Section: Discussionmentioning

confidence: 99%

Comparative effect of lurasidone and blonanserin on cortical glutamate, dopamine, and acetylcholine efflux: role of relative serotonin (5‐HT)_2A and DA D₂ antagonism and 5‐HT_1A partial agonism

Huang

Panos

Kwon

et al. 2013

Journal of Neurochemistry

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Atypical antipsychotic drugs (AAPDs) have been suggested to be more effective in improving cognitive impairment in schizophrenia than typical APDs, a conclusion supported by differences in receptor affinities and neurotransmitter efflux in the cortex and the hippocampus. More potent serotonin (5-HT) 2A than dopamine (DA) D 2 receptors antagonism, and direct or indirect 5-HT 1A agonism, characterize almost all AAPDs. Blonanserin, an AAPD, has slightly greater affinity for D 2 than 5-HT 2A receptors. Using microdialysis and ultra performance liquid chromatography-mass spectrometry/mass spectrometry, we compared the abilities of the typical APD, haloperidol, three AAPDs, blonanserin, lurasidone, and olanzapine, and a selective 5-HT 1A partial agonist, tandospirone, and all, except haloperidol, were found to ameliorate the cognitive deficits produced by the N-methyl-d-aspartate antagonist, phencyclidine, altering the efflux of neurotransmitters and metabolites in the rat cortex and nucleus accumbens. Blonanserin, lurasidone, olanzapine, and tandospirone, but not haloperidol, increased the efflux of cortical DA and its metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid. Olanzapine and lurasidone increased the efflux of acetylcholine; lurasidone increased glutamate as well. None of the compounds significantly altered the efflux of 5-HT or its metabolite, 5-hydroxyindole acetic acid, or GABA, serine, and glycine. The ability to increase cortical DA efflux was the only shared effect of the compounds which ameliorates the deficit in cognition in rodents following phencyclidine.

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“…Through coordinated modulation of potassium and calcium channels (Ben-Ari et al, 1992; Perez-Burgos et al, 2010), M 1 can shape the synaptic integration and spiking activity in MSNs. Correspondingly, muscarinic agonists, particularly those with M 1 -preferring activity (e.g., AC260584, sabcomeline, xanomeline) have been shown to acutely stimulate DA efflux within the PFC and striatum (Li et al, 2007; Li et al, 2008). Data from neuroimaging studies have demonstrated that frontal and striatal DA release is critical for working memory representations and behavioral flexibility, respectively (Cools and D’Esposito, 2011; Frank et al, 2001).…”

Section: 7 M1 Positive Allosteric Modulators (Pams)mentioning

confidence: 99%

Positive allosteric modulation of M 1 and M 4 muscarinic receptors as potential therapeutic treatments for schizophrenia

Yohn

Conn

2018

Neuropharmacology

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Current antipsychotic drugs provide symptomatic relief for positive symptoms of schizophrenia, but do not offer symptom management for negative and cognitive symptoms. In addition, many patients discontinue treatment due to adverse side effects. Therefore, there is a critical need to develop more effective and safe treatment options. Although the etiology of schizophrenia is unclear, considerable data from post-mortem, neuroimaging and neuropharmacology studies support a role of the muscarinic acetylcholine (mAChRs) in the pathophysiology of schizophrenia. Substantial evidence suggests that activation of mAChRs has the potential to treat all symptom domains of schizophrenia. Despite encouraging results in demonstrating efficacy, clinical trials of nonselective mAChR agonists were limited in their clinical utility due to dose-limiting peripheral side effects. Accordingly, efforts have been made to specifically target centrally located M and M mAChR subtypes devoid of adverse-effect liability. To circumvent this limitation, there have been tremendous advances in the discovery of ligands that bind at allosteric sites, binding sites distinct from the orthosteric site, which are structurally less conserved and thereby afford high levels of receptor subtype selectivity. The discovery of subtype-specific allosteric modulators has greatly advanced our understanding of the physiological role of various muscarinic receptor subtypes in schizophrenia and the potential utility of M and M mAChR subtypes as targets for the development of novel treatments for schizophrenia and related disorders. This article is part of the Special Issue entitled 'Neuropharmacology on Muscarinic Receptors'.

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Effect of muscarinic receptor agonists xanomeline and sabcomeline on acetylcholine and dopamine efflux in the rat brain; comparison with effects of 4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one (AC260584) and N-desmethylclozapine

Cited by 19 publications

References 53 publications

The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: A meta‐analysis

The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: A meta‐analysis

Comparative effect of lurasidone and blonanserin on cortical glutamate, dopamine, and acetylcholine efflux: role of relative serotonin (5‐HT)_2A and DA D₂ antagonism and 5‐HT_1A partial agonism

Positive allosteric modulation of M 1 and M 4 muscarinic receptors as potential therapeutic treatments for schizophrenia

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Effect of muscarinic receptor agonists xanomeline and sabcomeline on acetylcholine and dopamine efflux in the rat brain; comparison with effects of 4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one (AC260584) and N-desmethylclozapine

Cited by 19 publications

References 53 publications

The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: A meta‐analysis

The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: A meta‐analysis

Comparative effect of lurasidone and blonanserin on cortical glutamate, dopamine, and acetylcholine efflux: role of relative serotonin (5‐HT)2A and DA D2 antagonism and 5‐HT1A partial agonism

Positive allosteric modulation of M 1 and M 4 muscarinic receptors as potential therapeutic treatments for schizophrenia

Contact Info

Product

Resources

About

Comparative effect of lurasidone and blonanserin on cortical glutamate, dopamine, and acetylcholine efflux: role of relative serotonin (5‐HT)_2A and DA D₂ antagonism and 5‐HT_1A partial agonism