The influence of adenosine A3 receptor agonist: IB-MECA, on scopolamine- and MK-801-induced memory impairment

Rubaj, Andrzej; Zgodziński, Witold; Sieklucka-Dziuba, M

doi:10.1016/s0166-4328(02)00314-5

Cited by 34 publications

(16 citation statements)

References 47 publications

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“…48,49 This was accomplished by designing agonist nucleosides, with an awareness of the structural determinants of full agonism and of the preference for the (N)-ribose ring conformation in binding to the A 3 AR. The goal was to prepare novel, fully efficacious A 3 AR agonists having high affinity and selectivity.…”

Section: Discussionmentioning

confidence: 99%

(N)-Methanocarba 2,N⁶-Disubstituted Adenine Nucleosides as Highly Potent and Selective A₃ Adenosine Receptor Agonists

et al. 2004

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A series of ring-constrained (N)-methanocarba-5′-uronamide 2,N 6 -disubstituted adenine nucleosides have been synthesized via Mitsunobu condensation of the nucleobase precursor with a pseudosugar ring containing a 5′-ester functionality. Following appropriate functionalization of the adenine ring, the ester group was converted to the 5′-N-methylamide. The compounds, mainly 2-chloro substituted derivatives, were tested in both binding and functional assays at human adenosine receptors (ARs), and many were found to be highly potent and selective A 3 AR agonists. Selected compounds were compared in binding to the rat A 3 AR to assess their viability for testing in rat disease models. The N 6 -(3-chlorobenzyl) and N 6 -(3-bromobenzyl) analogues displayed K i values at the human A 3 AR of 0.29 and 0.38 nM, respectively. Other subnanomolar affinities were observed for the following N 6 derivatives: 2,5-dichlorobenzyl, 5-iodo-2-methoxybenzyl, trans-2-phenyl-1-cyclopropyl, and 2,2-diphenylethyl. Selectivity for the human A 3 AR in comparison to the A 1 AR was (fold): the N 6 -(2,2-diphenylethyl) analogue 34 (1900), the N 6 -(2,5-dimethoxybenzyl) analogue 26 (1200), the N 6 -(2,5-dichlorobenzyl) and N 6 -(2-phenyl-1-cyclopropyl) analogues 20 and 33 (1000), and the N 6 -(3-substituted benzyl) analogues 17, 18, 28, and 29 (700-900). Typically, even greater selectivity ratios were obtained in comparison with the A 2A and A 2B ARs. The (N)-methanocarba-5′-uronamide analogues were full agonists at the A 3 AR, as indicated by the inhibition of forskolin-stimluated adenylate cyclase at a concentration of 10 µM. The N 6 -(2,2-diphenylethyl) derivative was an A 3 AR agonist in the (N)-methanocarba-5′-uronamide series, although it was an antagonist in the ribose series. Thus, many of the previously known groups that enhance A 3 AR affinity in the 9-riboside series, including those that reducing intrinsic efficacy, may be adapted to the (N)-methanocarba nucleoside series of full agonists.

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Section: Discussionmentioning

confidence: 99%

(N)-Methanocarba 2,N⁶-Disubstituted Adenine Nucleosides as Highly Potent and Selective A₃ Adenosine Receptor Agonists

et al. 2004

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“…Impairment of learning and memory, as the most characteristic manifestation of dementia, can be induced chemically in experimental animals by scopolamine, a cholinergic antagonist known to interfere with acetylcholine transmission in the central nervous system (Misane and Ogren, 2003). The experimental animal model of scopolamine-induced amnesia has been extensively used to screen for compounds with potential therapeutic value in dementia (Bejar et al, 1999;Rubaj et al, 2003). Thus, we have tried to search for cognitive-enhancing compounds from natural resources by using scopolamine-induced memory impairment in mice.…”

Section: Introductionmentioning

confidence: 99%

Cognitive-enhancing activity of loganin isolated from Cornus officinalis in scopolamine-induced amnesic mice

et al. 2009

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We examined anti-amnesic activity of the methanolic extract of Cornus officinalis fruits (COT) and a major constituent, loganin using scopolamine-induced (1 mg/kg body weight, s.c.) amnesic mice with both passive avoidance and the Morris water maze tests. Oral treatment of mice with COT (100 mg/kg body weight) and loganin (1 and 2 mg/kg body weight) significantly mitigated scopolamine-induced memory deficits in passive avoidance test. In the Morris water maze test, oral treatment of loganin significantly ameliorated scopolamine-induced memory deficits showing the formation of long-term and/or short-term spatial memory. Moreover, loganin (2 mg/kg body weight) significantly inhibited acetylcholinesterase activity by as much as 45% of control in the mouse hippocampus. These results indicate that loganin may exert antiamnesic activity in in vivo through acetylcholinesterase inhibition.

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“…The benefit of various cholinergic agonists is now well established to cause reversal of Sco-induced amnesic effects in animals as well as humans. Sco-induced amnesia model has been used extensively to screen various potential antidementia drugs [18,19,[30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Effect of Sida Cordifolia L. Against Scopolamine-Induced Cognitive Deficit Mice Model

Khurana

Sharma

Patil

et al. 2017

Asian J Pharm Clin Res

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Objective: In this study, ameliorative effect of aqueous extracts of Sida cordifolia and hydroethanolic extracts of S. cordifolia L. (AESC and EESC, respectively) was evaluated against scopolamine (Sco)-induced amnesia in mice. S. cordifolia L. is a well-know Ayurvedic plant which has been administered anciently for various nervous disorders including loss of memory. Female Swiss albino mice were used for Sco-induced amnesia model and acute toxicity study.Methods: Acute toxicity study was carried out to select safe and effective doses (50, 100 and 250 mg/kg; p.o.) of AESC and EESC for further pharmacological evaluation. The AESC and EESC at selected doses and donepezil (Dpl) (5 mg/kg; p.o.) were administered to different groups for consecutive 15 days. On 15 th day of treatment, Sco (0.4 mg/kg, intraperitoneally) was administered to different groups for induction of amnesia. Mice were subjected to transfer latency (TL) and step down latency (SDL) tests on the 16 th day to evaluate the effect of AESC and EESC on memory.Results: Sco treatment caused a significant increase in TL and decrease in SDL. The EESC significantly and dose dependently reversed the Sco-induced amnesia. The maximum effect was seen in EESC (100 mg/kg) treated group. This effect of EESC was comparable to the group treated with Dpl. The group treated with varying doses of AESC showed no significant effect on TL and SDL. Conclusion:These findings suggested the possible therapeutic potential of EESC (70%) for diseases related to memory dysfunctions like dementia in Alzheimer's disease.

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The influence of adenosine A3 receptor agonist: IB-MECA, on scopolamine- and MK-801-induced memory impairment

Cited by 34 publications

References 47 publications

(N)-Methanocarba 2,N⁶-Disubstituted Adenine Nucleosides as Highly Potent and Selective A₃ Adenosine Receptor Agonists

(N)-Methanocarba 2,N⁶-Disubstituted Adenine Nucleosides as Highly Potent and Selective A₃ Adenosine Receptor Agonists

Cognitive-enhancing activity of loganin isolated from Cornus officinalis in scopolamine-induced amnesic mice

Ameliorative Effect of Sida Cordifolia L. Against Scopolamine-Induced Cognitive Deficit Mice Model

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The influence of adenosine A3 receptor agonist: IB-MECA, on scopolamine- and MK-801-induced memory impairment

Cited by 34 publications

References 47 publications

(N)-Methanocarba 2,N6-Disubstituted Adenine Nucleosides as Highly Potent and Selective A3 Adenosine Receptor Agonists

(N)-Methanocarba 2,N6-Disubstituted Adenine Nucleosides as Highly Potent and Selective A3 Adenosine Receptor Agonists

Cognitive-enhancing activity of loganin isolated from Cornus officinalis in scopolamine-induced amnesic mice

Ameliorative Effect of Sida Cordifolia L. Against Scopolamine-Induced Cognitive Deficit Mice Model

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Product

Resources

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(N)-Methanocarba 2,N⁶-Disubstituted Adenine Nucleosides as Highly Potent and Selective A₃ Adenosine Receptor Agonists

(N)-Methanocarba 2,N⁶-Disubstituted Adenine Nucleosides as Highly Potent and Selective A₃ Adenosine Receptor Agonists