A comparative analysis of the efficacy of neuromidin and galantamine in Alzheimer’s disease

Zhivolupov, S. A.; Rashidov, N. A.; Samartsev, I. N.; Jakovlev, E.V.

doi:10.17116/jnevro201511510222-27

Cited by 4 publications

(2 citation statements)

References 13 publications

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“…This drug was the subject of several studies published in Russian in this country, which have shown some therapy benefits for dementia patients [19][20][21][22]. The efficacy and safety of galantamine, which is frequently used in Russia, was also demonstrated [23][24][25].…”

Section: Discussionmentioning

confidence: 99%

Treatment Patterns of Patients with All-Cause Dementia in Russia

Kostev¹,

Osina²

2020

Journal of Alzheimer's Disease Reports

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Background: Studies on prevalence or the therapy of dementia are rare or non-existent in Russia. Objective: The purpose of this study was to analyze the prescription patterns of antidementia therapy in Russia in 2018. Methods: This retrospective cross-sectional study was based on the IQVIA Russia LRx database, which covers approximately 11% of all patients enrolled in federal or regional reimbursement state healthcare programs. We descriptively analyzed the proportions of patients treated with antidementia drugs, antipsychotics, antidepressants, and benzodiazepines. Results: A total of 12,051 dementia patients were available for analysis. Of those, 6,394 patients had a vascular dementia (VaD) diagnosis, while 3,413 were diagnosed with dementia in other diseases (DOD), 1,128 with Alzheimer's disease (AD), and 1,116 with unspecified dementia (UD). The therapy with the highest patient proportion was antipsychotics, with 74% of VaD patients, 73% of UD patients, and 47% of DOD patients receiving these drugs. The proportion of patients treated with antidementia drugs was 68% in AZ, 56% in VaD, 45% in UD, and only 9% in DOD. Antidepressants were a relatively rare therapy in dementia patients (between 4% and 12%), and 30% of DOD patients received benzodiazepines, while the proportions of patients receiving this therapy class in other dementias was low (7-10%). Most patients were treated with old-generation drugs. Conclusion:The proportion of older drugs prescribed in Russia is higher than in Western Europe, which may likely be due to their low prices, resulting in a higher chance for successful health insurance reimbursement claims.

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Section: Discussionmentioning

confidence: 99%

Treatment Patterns of Patients with All-Cause Dementia in Russia

Kostev¹,

Osina²

2020

Journal of Alzheimer's Disease Reports

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“…To create new homobivalent MTDLs within the present study, we used another anticholinesterase pharmacophore—the amiridine molecule. Amiridine is an anticholinesterase drug that has found use in Russia and some other countries in Eastern Europe as a therapeutic agent for AD and certain other neurological disorders [ 70 , 71 , 72 , 73 , 74 , 75 ]. Known to inhibit AChE and BChE, with more potency against the latter enzyme, amiridine also exhibits numerous other biological activities [ 76 , 77 ] that have been reviewed in our previous publication [ 78 ].…”

Section: Introductionmentioning

confidence: 99%

Bis-Amiridines as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: N-Functionalization Determines the Multitarget Anti-Alzheimer’s Activity Profile

et al. 2022

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Using two ways of functionalizing amiridine—acylation with chloroacetic acid chloride and reaction with thiophosgene—we have synthesized new homobivalent bis-amiridines joined by two different spacers—bis-N-acyl-alkylene (3) and bis-N-thiourea-alkylene (5) —as potential multifunctional agents for the treatment of Alzheimer’s disease (AD). All compounds exhibited high inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity for BChE. These new agents displayed negligible carboxylesterase inhibition, suggesting a probable lack of untoward drug–drug interactions arising from hydrolytic biotransformation. Compounds 3 with bis-N-acyl-alkylene spacers were more potent inhibitors of both cholinesterases compared to compounds 5 and the parent amiridine. The lead compounds 3a–c exhibited an IC50(AChE) = 2.9–1.4 µM, IC50(BChE) = 0.13–0.067 µM, and 14–18% propidium displacement at 20 mM. Kinetic studies of compounds 3a and 5d indicated mixed-type reversible inhibition. Molecular docking revealed favorable poses in both catalytic and peripheral AChE sites. Propidium displacement from the peripheral site by the hybrids suggests their potential to hinder AChE-assisted Aβ42 aggregation. Conjugates 3 had no effect on Aβ42 self-aggregation, whereas compounds 5c–e (m = 4, 5, 6) showed mild (13–17%) inhibition. The greatest difference between conjugates 3 and 5 was their antioxidant activity. Bis-amiridines 3 with N-acylalkylene spacers were nearly inactive in ABTS and FRAP tests, whereas compounds 5 with thiourea in the spacers demonstrated high antioxidant activity, especially in the ABTS test (TEAC = 1.2–2.1), in agreement with their significantly lower HOMO-LUMO gap values. Calculated ADMET parameters for all conjugates predicted favorable blood–brain barrier permeability and intestinal absorption, as well as a low propensity for cardiac toxicity. Thus, it was possible to obtain amiridine derivatives whose potencies against AChE and BChE equaled (5) or exceeded (3) that of the parent compound, amiridine. Overall, based on their expanded and balanced pharmacological profiles, conjugates 5c-e appear promising for future optimization and development as multitarget anti-AD agents.

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Conjugates of amiridine and salicylic derivatives as promising multifunctional CNS agents for potential treatment of Alzheimer's disease

Makhaeva,

Grishchenko,

Kovaleva

et al. 2024

Archiv der Pharmazie

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New conjugates of amiridine and salicylic derivatives (salicylamide, salicylimine, and salicylamine) with different lengths of alkylene spacers were designed, synthesized, and evaluated as potential multifunctional central nervous system therapeutic agents for Alzheimer's disease (AD). Conjugates demonstrated high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition (IC50: AChE, 0.265−4.24 μM; BChE, 0.01−0.64 μM) but poor activity against off‐target carboxylesterase (CES). Specifically, conjugates with a (CH2)8 spacer showed the highest AChE and BChE inhibition: 3–16 times more effective than amiridine. Salicylamides 7b and 7c had the maximum BChE/AChE selectivity ratios: 193 and 138, respectively. Conjugates were mixed‐type reversible inhibitors of both cholinesterases and displaced propidium from the AChE peripheral anionic site (PAS) at the level of donepezil. All conjugates inhibited Aβ42 self‐aggregation in the thioflavin test; inhibition increased with spacer elongation, being greatest for (CH2)8. The results agreed with molecular docking to AChE, BChE, and Aβ42. Conjugates exhibited high 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS)•+‐scavenging activity comparable to the standard antioxidant Trolox, and they showed the ability to bind Cu2+, Fe2+, and Zn2+. Conjugates had favorable predicted intestinal absorption and blood–brain barrier permeability. Altogether, the results indicate that the new conjugates possess potential for further development as multifunctional anti‐AD drug candidates.

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A comparative analysis of the efficacy of neuromidin and galantamine in Alzheimer’s disease

Abstract: The results suggest that the effectiveness of anticholinesterase treatment of Alzheimer's disease could be determined not only by the central but also peripheral cholinergic action.

Cited by 4 publications

References 13 publications

Treatment Patterns of Patients with All-Cause Dementia in Russia

Treatment Patterns of Patients with All-Cause Dementia in Russia

Bis-Amiridines as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: N-Functionalization Determines the Multitarget Anti-Alzheimer’s Activity Profile

Conjugates of amiridine and salicylic derivatives as promising multifunctional CNS agents for potential treatment of Alzheimer's disease

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