The dual-acting AChE inhibitor and H3 receptor antagonist UW-MD-72 reverses amnesia induced by scopolamine or dizocilpine in passive avoidance paradigm in rats

Sadek, Bassem; Khan, Nadia; Darras, Fouad H.; Pockes, Steffen; Decker, Michael

doi:10.1016/j.physbeh.2016.08.022

Cited by 35 publications

(49 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ability of scopolamine to impair memory is characterized by dysfunction of the central cholinergic system of neurotransmission, impaired neuronal antioxidant status, and alteration in functional neurochemistry (Akinyemi et al., ; El‐Khadragy et al., ; Goverdhan, Sravanthi, & Mamatha, ). This has therefore made scopolamine a useful drug in simulating human dementia and AD (Akinyemi et al., ; Kwon, Kim, Lee, & Jang, ; Sadek, Khan, Darras, Pockes, & Decker, ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Green leafy vegetables from two Solanum spp. (Solanum nigrum L and Solanum macrocarpon L) ameliorate scopolamine‐induced cognitive and neurochemical impairments in rats

Ogunsuyi

Ademiluyi

Oboh

et al. 2018

Food Science & Nutrition

View full text Add to dashboard Cite

This study examined the modulatory effect of Black nightshade (Solanum nigrum L) and African eggplant (Solanum macrocarpon L) leaves on cognitive function, antioxidant status, and activities of critical enzymes of monoaminergic and cholinergic systems of neurotransmission in scopolamine‐administered rats. Cognitive impairment was induced in albino rats pretreated with dietary inclusions of Black nightshade (BN) and African eggplant (AE) leaves by single administration (i.p.) of scopolamine (2 mg/kg body weight). Prior to termination of the experiment, the rats were subjected to spontaneous alternation (Y‐maze) test to assess their spatial working memory. Thereafter, activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO), arginase, and antioxidant enzymes (catalase, SOD, and GST) of rat brain homogenate were determined. Also, the malondialdehyde (MDA), nitrite, and GSH contents of the homogenate were determined. The results showed that pretreatment with dietary inclusions of AE and BN significantly reversed the impairment in the rats’ spatial working memory induced by scopolamine. Similarly, elevations in activities of AChE, BChE, and MAO induced by scopolamine were significantly reversed in rats pretreated with dietary inclusions of AE and BN. In addition, impaired antioxidant status induced by scopolamine was reversed by pretreatment with dietary inclusions of AE and BN. This study has shown that dietary inclusions of AE and BN could protect against cognitive and neurochemical impairments induced by scopolamine, and hence, these vegetables could be used as a source of functional foods and nutraceuticals for the prevention and management of cognitive impairments associated diseases such as Alzheimer's disease.

show abstract

Section: Introductionmentioning

confidence: 99%

“…This has therefore made scopolamine a useful drug in simulating human dementia and AD Kwon, Kim, Lee, & Jang, 2009;Sadek, Khan, Darras, Pockes, & Decker, 2016).…”

Section: Introductionmentioning

confidence: 99%

Green leafy vegetables from two Solanum spp. (Solanum nigrum L and Solanum macrocarpon L) ameliorate scopolamine‐induced cognitive and neurochemical impairments in rats

Ogunsuyi

Ademiluyi

Oboh

et al. 2018

Food Science & Nutrition

View full text Add to dashboard Cite

show abstract

“…Its activity in the synaptic cleft is controlled by cholinesterase enzymes, responsible for the termination of acetylcholine biological activity through its hydrolysis in cholinergic synapses (Bajda et al, ; Darras et al, ; Lazewska et al, ). Currently, the pharmacotherapy of AD relies on the use of four marketed drugs, namely donepezil, rivastigmine and galantamine, as cholinesterase inhibitors, and the NMDA receptor antagonist memantine (Chen et al, ; Lalut et al, ; Sadek, Khan, Darras, Pockes, & Decker, ). However, these disease‐modifying agents only alleviate temporally the AD clinical symptoms, while their efficacy as monotherapy is one of today's controversial issues in AD.…”

Section: Introductionmentioning

confidence: 99%

In silico and in vitro studies of two non‐imidazole multiple targeting agents at histamine H₃ receptors and cholinesterase enzymes

et al. 2019

View full text Add to dashboard Cite

Recently, multi-target directed ligands have been of research interest for multifactorial disorders such as Alzheimer's disease (AD). Since H 3 receptors (H 3 Rs) and cholinesterases are involved in pathophysiology of AD, identification of dual-acting compounds capable of improving cholinergic neurotransmission is of importance in AD pharmacotherapy. In the present study, H 3 R antagonistic activity combined with anticholinesterase properties of two previously computationally identified leadpropyl]-1H-indole-2-carboxamide) and compound 4 (7-chloro-N-[(1-methylpiperidin-3-yl)methyl]-1,2,3,4-tetrahydroisoquinoline-2-carboxamide), was tested.Moreover, molecular docking and binding free energy calculations were conducted for binding mode and affinity prediction of studied ligands toward cholinesterases. Biological evaluations revealed inhibitory activity of ligands in nanomolar (com-pound 3: H 3 R EC 50 = 0.73 nM; compound 4: H 3 R EC 50 = 31 nM) and micromolar values (compound 3: AChE IC 50 = 9.09 µM, BuChE IC 50 = 21.10 µM; compound 4: AChE IC 50 = 8.40 µM, BuChE IC 50 = 4.93 µM) for H 3 R antagonism and cholinesterase inhibition, respectively. Binding free energies yielded good consistency with cholinesterase inhibitory profiles. The results of this study can be used for lead optimization where dual inhibitory activity on H 3 R and cholinesterases is needed. Such ligands can exert their biological activity in a synergistic manner resulting in higher potency and efficacy. K E Y W O R D S anticholinesterase, anti-H 3 R agents, histamine H 3 receptor, molecular docking, molecular dynamics simulation, multi-target directed ligands 280 | GHAMARI et Al.

show abstract

“…The first antihistamines at the histamine H 1 receptor (H 1 R) were already developed in the early 1930s and are still used for the treatment of histamine‐mediated allergic conditions . While H 2 R antagonists have been successfully used for the treatment of peptic ulcers, H 3 R is widely expressed in the central nervous system (CNS) and is still a potential drug target for, for example, neurodegenerative diseases . In 2016, Pitolisant became the first marketed histamine H 3 R inverse agonist/antagonist for the treatment of narcolepsy .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of heteroalicyclic cyanoguanidines at histamine receptors

Soliman

Wang

Zagotto

et al. 2019

Archiv der Pharmazie

Self Cite

View full text Add to dashboard Cite

Recent studies on histamine receptor (HR) subtypes identified imidazolyl butyl cyanoguanidines, like UR-PI376, as highly potent agonists at the human histamine H 4 receptor (hH 4 R). While imidazole-containing compounds display drawbacks in pharmacokinetics, we studied the possibility of replacing the heteroaromatic cycle by nonaromatic six-membered heterocycles (piperidine, morpholine, thiomorpholine, and N-methylpiperazine) as potential bioisosteres. Beyond that, this approach should give more information about the indispensability of the aromatic ring as a basic head group. Besides these changes, a variation of the spacer length (C 3 -C 5 ) connecting the heterocycle and the cyanoguanidine moiety has been made to possibly trigger the selectivity towards the respective HRs. Investigations in radioligand-binding assays exhibited only very weak activity at the hH 1 R and hH 3 R, while nearly all compounds were inactive at the hH 2 R and hH 4 R. In the case of piperidine-containing compounds, moderate affinities at the hH 3 R over the single-digit micromolar range were detected. K E Y W O R D S

show abstract

The dual-acting AChE inhibitor and H3 receptor antagonist UW-MD-72 reverses amnesia induced by scopolamine or dizocilpine in passive avoidance paradigm in rats

Cited by 35 publications

References 58 publications

Green leafy vegetables from two Solanum spp. (Solanum nigrum L and Solanum macrocarpon L) ameliorate scopolamine‐induced cognitive and neurochemical impairments in rats

Green leafy vegetables from two Solanum spp. (Solanum nigrum L and Solanum macrocarpon L) ameliorate scopolamine‐induced cognitive and neurochemical impairments in rats

In silico and in vitro studies of two non‐imidazole multiple targeting agents at histamine H₃ receptors and cholinesterase enzymes

Synthesis and biological evaluation of heteroalicyclic cyanoguanidines at histamine receptors

Contact Info

Product

Resources

About

The dual-acting AChE inhibitor and H3 receptor antagonist UW-MD-72 reverses amnesia induced by scopolamine or dizocilpine in passive avoidance paradigm in rats

Cited by 35 publications

References 58 publications

Green leafy vegetables from two Solanum spp. (Solanum nigrum L and Solanum macrocarpon L) ameliorate scopolamine‐induced cognitive and neurochemical impairments in rats

Green leafy vegetables from two Solanum spp. (Solanum nigrum L and Solanum macrocarpon L) ameliorate scopolamine‐induced cognitive and neurochemical impairments in rats

In silico and in vitro studies of two non‐imidazole multiple targeting agents at histamine H3 receptors and cholinesterase enzymes

Synthesis and biological evaluation of heteroalicyclic cyanoguanidines at histamine receptors

Contact Info

Product

Resources

About

In silico and in vitro studies of two non‐imidazole multiple targeting agents at histamine H₃ receptors and cholinesterase enzymes