Dual Target Ligands with 4-tert-Butylphenoxy Scaffold as Histamine H3 Receptor Antagonists and Monoamine Oxidase B Inhibitors

Łażewska, Dorota; Olejarz-Maciej, Agnieszka; Reiner, David J.; Kaleta, Maria; Latacz, Gniewomir; Zygmunt, Małgorzata; Doroż-Płonka, Agata; Karcz, Tadeusz; Frank, Annika; Stark, Holger; Kieć‐Kononowicz, Katarzyna

doi:10.3390/ijms21103411

Cited by 15 publications

(31 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(Trevitt et al., 2009; Maj et al., 1990; Juszkiewicz et al., 1994; Juszkiewicz et al., 1995; Mandhane et al., 1997; Konieczny et al., 1999; Jagtap & Inamdar, 2001; Ossowska et al., 2001; Breysse et al., 2002; Moo‐Puc et al., 2003; Ossowska et al., 2003; Rukoyatkina et al., 2003; Wardas et al., 2003; Tanganelli et al., 2004; Ossowska et al., 2005; Zazpe et al., 2006; Lopez et al., 2007; Sibille et al., 2007; Ahemad et al., 2009; Beurrier et al., 2009; Góngora‐Alfaro et al., 2009; Konieczny et al., 2009; Ardashov et al., 2011; Joshi et al., 2011; Trevizol et al., 2011; Lopez et al., 2012; Shyamjith et al., 2012; Goudet et al., 2012; Acuña‐Lizama et al., 2013; Konieczny & Lenda, 2013; Atack et al., 2014; Ittiyavira & Ruby, 2014; Azam, et al., 2009; Zheng et al., 2014; Gmiro et al., 2015; Maurice et al., 2015; Nade et al., 2015; Bhangale & Acharya, 2016; Dhingra & Gahalain, 2016; Basu et al., 2017; Chitra et al., 2017; Gupta et al., 2017; Kumari et al., 2017; Kronbauer et al., 2017; Tian et al., 2017; Yang et al., 2016; Engelhardt et al., 2018; Slee et al., 2008; Saleem et al., 2019; Kabra et al., 2020; Łażewska et al., 2020; Chiu et al., 1981; Schmidt & Bubser, 1989; Schmidt et al., 1991; Kretschmer, 1994; Kretschmer et al.,…”

Section: Resultsmentioning

confidence: 99%

“…The variation in publications per year is important data. As noted, the haloperidol‐induced catalepsy model for parkinsonism was first applied in the early 1980s (Chiu et al., 1981; Pycock et al., 1982; Schallert & Teitelbaum, 1981; Scheel‐Krüger & Magelund, 1981) and is still widely used nowadays (Bhattamisra et al., 2020; Chaudhary & Dhande, 2020; Kabra et al., 2020; Łażewska et al., 2020; Olaya et al., 2020; Parambi et al., 2020; Pardo et al., 2020; Sanawar et al., 2020; Sharma et al., 2020; Sita et al., 2020). In fact, since 2000, the number of articles published using this model has increased and become more constant (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…Although responses to haloperidol vary widely among studies, the cataleptic effects of haloperidol emerge especially at doses of 0.5 mg/kg and higher (Ionov et al., 2018; Ionov & Severtsev, 2012a; Koranda et al., 2016; Luthra et al., 2008; Mandhane et al., 1997; Marazziti et al., 2007). The most used dose was 1.0 mg/kg, capable of inducing catalepsy regardless of the species or strain used (Darbaky et al., 2003; Kasture, Suvarna, et al., 2009; Łażewska et al., 2020; Melo‐Thomas & Thomas, 2015). The prevalence of the 1.0 mg/kg dose can be justified by the fact that, although haloperidol dose should induce catalepsy, it is important to avoid excessive doses that could make it difficult to observe catalepsy reversals by potential therapeutics.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Haloperidol‐induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies

Waku

Magalhães

Alves

et al. 2021

Eur J of Neuroscience

View full text Add to dashboard Cite

Several useful animal models for parkinsonism have been developed so far. Haloperidol‐induced catalepsy is often used as a rodent model for the study of motor impairments observed in Parkinson's disease and related disorders and for the screening of potential antiparkinsonian compounds. The objective of this systematic review is to identify publications that used the haloperidol‐induced catalepsy model for parkinsonism and to explore the methodological characteristics and the main questions addressed in these studies. A careful systematic search of the literature was carried out by accessing articles in three different databases: Web of Science, PubMed and SCOPUS. The selection and inclusion of studies were performed based on the abstract and, subsequently, on full‐text analysis. Data extraction included the objective of the study, study design and outcome of interest. Two hundred and fifty‐five articles were included in the review. Publication years ranged from 1981 to 2020. Most studies used the model to explore the effects of potential treatments for parkinsonism. Although the methodological characteristics used are quite varied, most studies used Wistar rats as experimental subjects. The most frequent dose of haloperidol used was 1.0 mg/kg, and the horizontal bar test was the most used to assess catalepsy. The data presented here provide a framework for an evidence‐based approach to the design of preclinical research on parkinsonism using the haloperidol‐induced catalepsy model. This model has been used routinely and successfully and is likely to continue to play a critical role in the ongoing search for the next generation of therapeutic interventions for parkinsonism.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Haloperidol‐induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies

Waku

Magalhães

Alves

et al. 2021

Eur J of Neuroscience

View full text Add to dashboard Cite

show abstract

“…Inhibitory potency of compound 1 and 8 on MAO-B isoenzyme was tested fluorometrically with a commercial Amplex™ Red Monoamine Oxidase Assay Kit (Thermo Fisher Scientific A12214, Waltham, MA, USA) as we reported previously [ 46 , 68 ]. Human MAO-B was purchased from Merck KGaA (Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity—In Vitro and In Vivo Studies

et al. 2022

Self Cite

View full text Add to dashboard Cite

Trying to meet the multitarget-directed ligands strategy, a series of previously described aryl-substituted phenylalanine derivatives, reported as competitive antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, were screened in vitro for their free-radical scavenging and antioxidant capacity in two different assays: ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity fluorescent (ORAC-FL) assays. The most active antioxidants 1 and 8 were further examined to evaluate their neuroprotective properties in vitro. In this study, compound 1 showed a significant neuroprotective effect against the neurotoxin 6-hydroxydopamine in neuroblastoma SH-SY5Y and IMR-32 cell lines. Both compounds also showed prevention from high levels of reactive oxygen species (ROS) in SH-SY5Y cells. Furthermore, the desired monoamine oxidase B (MAO-B) inhibition effect (IC50 = 278 ± 29 nM) for 1 was determined. No toxic effects up to 100 µM of 1 and 8 against neuroblastoma cells were observed. Furthermore, in vivo studies showed that compound 1 demonstrated significant anticonvulsant potential in 6-Hz test, but in neuropathic pain models its antiallodynic and antihyperalgesic properties were not observed. Concluding, the compound 1 seems to be of higher importance as a new phenylalanine-based lead candidate due to its confirmed promise in in vitro and in vivo anticonvulsant activity.

show abstract

“…The signal was measured after 1h (excitation at 570 nm and emission at 585 nm) using EnSpire® multimode plate reader (Perkin Elmer, Inc.). Rasagiline (1 µM) or clorgyline (1 µM) were tested as reference compounds for MAO-B and MAO-A inhibitions, respectively 58,59.…”

mentioning

confidence: 99%

A dual-acting 5-HT6 receptor inverse agonist/MAO-B inhibitor displays glioprotective and pro-cognitive properties

Canale

Grychowska

Kurczab

et al. 2020

European Journal of Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

The complex etiology of Alzheimer's disease has initiated a quest for multi-target ligands to address the multifactorial causes of this neurodegenerative disorder. In this context, we designed dual-acting 5-HT6 receptor (5-HT6R) antagonists/MAO-B inhibitors using pharmacophore hybridization strategy. Our approach involved linking 5-HT6R scaffolds with aryloxy fragments derived from reversible and irreversible MAO-B inhibitors. The study identified compound 48 that acts as an inverse agonist of 5-HT6R at Gs signaling and an irreversible MAO-B inhibitor. Compound 48 showed moderate metabolic stability in rat microsomal assay and artificial membrane permeability, and it was well distributed to the brain. Additionally, 48 showed glioprotective properties in a model of cultured astrocytes using 6-OHDA as the cytotoxic agent. Finally, compound 48 (MED = 1 mg/kg, p.o.) fully reversed memory deficits in the NOR task induced by scopolamine in rats. A better understanding of effects exerted by dual-acting 5-HT6R/MAO-B modulators may impact the future development of neurodegenerative-directed treatment strategies.

show abstract

Dual Target Ligands with 4-tert-Butylphenoxy Scaffold as Histamine H3 Receptor Antagonists and Monoamine Oxidase B Inhibitors

Cited by 15 publications

References 29 publications

Haloperidol‐induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies

Haloperidol‐induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies

Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity—In Vitro and In Vivo Studies

A dual-acting 5-HT6 receptor inverse agonist/MAO-B inhibitor displays glioprotective and pro-cognitive properties

Contact Info

Product

Resources

About