Beta and gamma carboline derivatives as potential anti-Alzheimer agents: A comparison

Otto, Robert; Penzis, Robert; Gaube, Friedemann; Winckler, Thomas; Appenroth, Dorothea; Fleck, Christian; Tränkle, Christian; Lehmann, Jochen; Enzensperger, Christoph

doi:10.1016/j.ejmech.2014.09.048

Cited by 75 publications

(36 citation statements)

References 29 publications

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“…β-carbolines and γ-carbolines came into attention of anti-neurodegenerative drug designers due to the assorted activities of harmala alkaloids (harmaline, harmine, harmane, etc. ), which are β-carbolines, as well as by introducing the synthetic compounds with γ-carboline scaffold in pre-clinical and clinical research: dimebon (latrepirdine), karbidine, stobadine, flutroline [13,14,15]. As an indole scaffold occurs in the structure of known TRIs, such as (3a,7a)-3a-(3,4-dichlorophenyl)-2-methyloctahydro-1 H -isoindole and (3aS,6aR)-3a-(3,4-dichlorophenyl)-2-methyloctahydrocyclopenta[c]pyrrole [16], we decided to test antidepressant-like properties based on 5-HT, norepinephrine, and dopamine reuptake inhibition.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiology and Behavioral Assessment of the New Molecule SMe1EC2M3 as a Representative of the Future Class of Triple Reuptake Inhibitors

et al. 2019

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SMe1EC2M3 is a pyridoindole derivative related to the neuroleptic drug carbidine. Based on the structural similarities of SMe1EC2M3 and known serotonin (5-HT), norepinephrine, and dopamine reuptake inhibitors, we hypothesized that this compound may also have triple reuptake inhibition efficacy and an antidepressant-like effect. PreADMET and Dragon software was used for in silico prediction of pharmacokinetics and pharmacodynamics of SMe1EC2M3. Forced swim test was used to evaluate its antidepressant-like effects. Extracellular in vivo electrophysiology was used to assess 5-HT, norepinephrine, and dopamine reuptake inhibition efficacy of SMe1EC2M3. PreADMET predicted reasonable intestinal absorption, plasma protein binding, and blood-brain permeability for SMe1EC2M3. Dragon forecasted its efficiency as an antidepressant. Using behavioral measurements, it was found that SMe1EC2M3 decreased immobility time and increase swimming time during the forced swim test (FST). Electrophysiological investigations showed that SMe1EC2M3 dose-dependently suppressed the excitability of 5-HT neurons of the dorsal raphe nucleus (DRN), norepinephrine neurons of the locus coeruleus (LC), and dopamine neurons of the ventral tegmental area (VTA). The SMe1EC2M3-induced suppression of 5-HT, norepinephrine, and dopamine neurons was reversed by the antagonists of serotonin-1A (5-HT1A; WAY100135), α-2 adrenergic (α2, yohimbine), and dopamine-2 receptors (D2, haloperidol), respectively. We conclude that SMe1EC2M3 is prospective triple 5-HT, norepinephrine, and dopamine reuptake inhibitor with antidepressant-like properties, however future studies should be performed to complete the pharmacological profiling of this compound.

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Section: Introductionmentioning

confidence: 99%

Electrophysiology and Behavioral Assessment of the New Molecule SMe1EC2M3 as a Representative of the Future Class of Triple Reuptake Inhibitors

et al. 2019

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“…The two pathological hallmarks of AD include senile plaques consisting beta-amyloid peptides and neurofibrillary tangles formed by hyperphosphorylation and abnormal deposition of tau proteins [2]. Multifactorial causes require multi-targeted treatment concepts [3]. AD is associated with an impairment of daily activities, behavior disturbances, and a variety of neuropsychiatric symptoms [4].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Inhaled Pimpinella peregrina Essential Oil on Scopolamine-Induced Memory Impairment, Anxiety, and Depression in Laboratory Rats

et al. 2016

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In the present study, we identified the effects of inhaled Pimpinella peregrina essential oil (1 and 3 %, for 21 continuous days) on scopolamine-induced memory impairment, anxiety, and depression in laboratory rats. Y-maze and radial arm-maze tests were used for assessing memory processes. Also, the anxiety and depressive responses were studied by means of the elevated plus-maze and forced swimming tests. The scopolamine alone-treated rats exhibited the following: decrease of the spontaneous alternation percentage in Y-maze test, increase of the number of working and reference memory errors in radial arm-maze test, along with decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. Inhalation of the P. peregrina essential oil significantly improved memory formation and exhibited anxiolytic- and antidepressant-like effects in scopolamine-treated rats. Our results suggest that the P. peregrina essential oil inhalation ameliorates scopolamine-induced memory impairment, anxiety, and depression. Moreover, studies on the P. peregrina essential oil may open a new therapeutic window for the prevention of neurological abnormalities closely related to Alzheimer's disease.

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“…Specifically, we cannot rule out the possibility that the actual used drugs against AD or PD can be recognized as substrates of brain GSTs or at least inducers of GSH-related enzymes via Kelch-like ECH-associated protein 1/nuclear factorerythroid 2 p45-related factor 2 (Keap1/Nrf2) pathways (Higgins and Hayes, 2011). A large number of putative drugs or drugmolecular targets are cited in the recent literature including nitric oxide synthase (NOS) inhibitors (Maher et al, 2014), pyruvate (Isopi et al, 2014), extracellular matrix molecules (Berezin et al, 2014), ginger components (Azam et al, 2014), cholinesterase inhibitors (Otto et al, 2014), anti-inflammatory drugs (Wang et al, 2015), insulin (Sebastião et al, 2014), etc. We should also mention a possible role of certain bio-metals involved in memory enhancement (zinc) or associated with amyloid precursor protein (APP) (copper) in AD (Parker et al, 2012).…”

Section: Cys47 Cys101mentioning

confidence: 99%

Glutathione transferases and neurodegenerative diseases

Mazzetti

Fiorile

Primavera

et al. 2015

Neurochemistry International

107

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Beta and gamma carboline derivatives as potential anti-Alzheimer agents: A comparison

Cited by 75 publications

References 29 publications

Electrophysiology and Behavioral Assessment of the New Molecule SMe1EC2M3 as a Representative of the Future Class of Triple Reuptake Inhibitors

Electrophysiology and Behavioral Assessment of the New Molecule SMe1EC2M3 as a Representative of the Future Class of Triple Reuptake Inhibitors

The Effects of Inhaled Pimpinella peregrina Essential Oil on Scopolamine-Induced Memory Impairment, Anxiety, and Depression in Laboratory Rats

Glutathione transferases and neurodegenerative diseases

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