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Chemical Compound Review

SureCN2763     (2S,3S)-2,3- dihydroxybutanedioic acid; [3...

Synonyms: ENA-713, ENA 713, FT-0656529, AC1L2U8Z, Tox21_112528, ...
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Disease relevance of Exelon


Psychiatry related information on Exelon

  • Thus, these findings suggest that ENA-713 may have protective, neurotrophic and therapeutic effects on aging-induced cholinergic dysfunction and be useful for the treatment of aging-related dementia, such as the Alzheimer-type dementia [5].
  • A novel brain-selective acetylcholinesterase inhibitor, SDZ ENA 713, is under development for the treatment of dementia of the Alzheimer type [6].
  • CONCLUSION: ENA 713 reversed the working memory deficit induced by scopolamine [7].

High impact information on Exelon

  • Moreover, although choline acetyltransferase (ChAT) activity was also significantly decreased in these four regions, it recovered in the frontal cortex, hippocampus and thalamus+midbrain after ENA-713 treatment [5].
  • In the senescent group, the acetylcholine (ACh) level was markedly reduced in the frontal cortex, hippocampus, striatum and thalamus+midbrain, but these reductions were completely prevented by ENA-713 [5].
  • The effects of chronic administration of ENA-713, an acetylcholinesterase (AChE) inhibitor, on pre- and postsynaptic cholinergic indices were examined in the senescent rat brain [5].
  • The maximum number (Bmax) of muscarinic M1 receptor (M1-R) binding site in the frontal cortex in the senescent group was decreased without any change in affinity, but this decrease was also inhibited by ENA-713 [5].
  • This study was designed to assess the effects of rivastigmine (Exelon) on the cognitive functioning of patients suffering from dementia with Lewy bodies [8].

Chemical compound and disease context of Exelon


Biological context of Exelon

  • RESULTS: Oral doses of [14C]SDZ ENA 713 were rapidly (tmax = 0.83 hr) and efficiently (ca. 93%) absorbed, although the bioavailability of the parent drug was low, ca. 0.5%, apparently due to extensive first-pass metabolism [9].
  • The present study compared the pharmacokinetics of [14C]SDZ ENA 713 after intravenous, oral, and dermal administration to male minipigs, and also examined the effects of dose level and skin abrasion on transdermal absorption [9].

Anatomical context of Exelon

  • Single oral administration of the acetylcholinesterase inhibitor SDZ ENA 713 (rivastigmine (+)-(S)-N-ethyl-3-[(1-dimethylamino)ethyl]-N-methylphenylcarbamate hydrogen tartrate) increases basal and K(+)-stimulated pyrrolidone carboxyl peptidase (Pcp) activity in mice frontal cortex synaptosomes in a dose-dependent manner [11].
  • In addition, histological experiment indicated that ENA-713 inhibited ischemia-induced pyramidal cell loss in the hippocampal CA1 regions [3].
  • Effects of SDZ ENA 713, novel acetyl cholinesterase inhibitor, on learning of rats with basal forebrain lesions [12].
  • However, post-ischemic administration of ENA-713 (three times 0.2 mg/kg, i.p.) significantly ameliorated this ischemia-induced decrease in the number of pyramidal cells by 47% of sham-operated controls, furthermore, it reduced the ischemia-induced accumulation of GFAP-positive astrocyte in the CA1 region [13].

Associations of Exelon with other chemical compounds


Gene context of Exelon

  • The effect of acetylcholinesterase inhibitor (SDZ ENA 713) for r-CBF and focal cerebral ischaemia [16].
  • Effects of Exelon on cognition were evaluated using the mini-mental state examination (MMSE) and selected items of Alzheimer's disease assessment scale (ADAS-cog) and the staging of the disease was measured using the global deterioration scale (GDS) [17].

Analytical, diagnostic and therapeutic context of Exelon

  • After dermal administration of [14C]SDZ ENA 713 to a virgin skin site, absorption was 8% at both dose levels investigated [9].
  • 4. Intraperitoneal injection of 0.10-0.05 mg/kg/day SDZ ENA 713 to the BF-lesioned rats showed amelioration of the learning impairment, with a decreased number of trials required to obtain 300-second-latency as well as an increase in the latency time after repeated training [12].
  • We examined by morphological methodology the effect of (S)-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methyl-phenylcarbamate hydrogentartrate (ENA-713), an acetylcholinesterase (AChE) inhibitor, on ischemia-induced neuronal death in the gerbil hippocampus due to a 5-min ligation of bilateral common carotid arteries after light ether anesthesia [13].
  • SEARCH STRATEGY: The Cochrane Controlled Trials Register, the Dementia Group Register of Clinical Trials, other electronic databases and other sources of reports were searched using the terms ENA 713, EXELON, and rivastigmine in addition to the terms for controlled trials in dementia (see the Group's search strategy for full details) [18].


  1. Inhibition of acetylcholinesterase modulates the autoregulation of cerebral blood flow and attenuates ischemic brain metabolism in hypertensive rats. Sadoshima, S., Ibayashi, S., Fujii, K., Nagao, T., Sugimori, H., Fujishima, M. J. Cereb. Blood Flow Metab. (1995) [Pubmed]
  2. Pharmacological evaluation of phenyl-carbamates as CNS-selective acetylcholinesterase inhibitors. Weinstock, M., Razin, M., Chorev, M., Enz, A. J. Neural Transm. Suppl. (1994) [Pubmed]
  3. Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia. Tanaka, K., Ogawa, N., Mizukawa, K., Asanuma, M., Kondo, Y., Nishibayashi, S., Mori, A. Neurochem. Res. (1994) [Pubmed]
  4. Effect of donepezil hydrochloride (E2020) on extracellular acetylcholine concentration in the cerebral cortex of rats. Kosasa, T., Kuriya, Y., Yamanishi, Y. Jpn. J. Pharmacol. (1999) [Pubmed]
  5. Chronic administration of acetylcholinesterase inhibitor in the senescent rat brain. Tanaka, K., Ogawa, N., Asanuma, M., Kondo, Y., Mori, A. Neurobiol. Aging (1994) [Pubmed]
  6. Effects of the novel acetylcholinesterase inhibitor SDZ ENA 713 on sleep in man. Holsboer-Trachsler, E., Hatzinger, M., Stohler, R., Hemmeter, U., Gray, J., Müller, J., Kocher, R., Spiegel, R. Neuropsychopharmacology (1993) [Pubmed]
  7. The acetylcholinesterase inhibitor, ENA 713 (Exelon), attenuates the working memory impairment induced by scopolamine in an operant DNMTP task in rats. Ballard, T.M., McAllister, K.H. Psychopharmacology (Berl.) (1999) [Pubmed]
  8. Effects of rivastigmine on cognitive function in dementia with lewy bodies: a randomised placebo-controlled international study using the cognitive drug research computerised assessment system. Wesnes, K.A., McKeith, I.G., Ferrara, R., Emre, M., Del Ser, T., Spano, P.F., Cicin-Sain, A., Anand, R., Spiegel, R. Dementia and geriatric cognitive disorders. (2002) [Pubmed]
  9. Absorption, metabolism, and disposition of [14C]SDZ ENA 713, an acetylcholinesterase inhibitor, in minipigs following oral, intravenous, and dermal administration. Tse, F.L., Laplanche, R. Pharm. Res. (1998) [Pubmed]
  10. Cholinesterase inhibitors for Alzheimer's disease. Birks, J. Cochrane database of systematic reviews (Online) (2006) [Pubmed]
  11. Acetylcholinesterase inhibitor SDZ ENA 713 (Rivastigmine) increases brain pyrrolidone carboxyl peptidase activity. Ramírez-Expósito, M.J., Robert-Baudouy, J., Mayas, M.D., García, M.J., Ramírez, M., Martínez-Martos, J.M. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. (2001) [Pubmed]
  12. Effects of SDZ ENA 713, novel acetyl cholinesterase inhibitor, on learning of rats with basal forebrain lesions. Niigawa, H., Tanimukai, S., Takeda, M., Hariguchi, S., Nishimura, T. Prog. Neuropsychopharmacol. Biol. Psychiatry (1995) [Pubmed]
  13. Post-ischemic administration of the acetylcholinesterase inhibitor ENA-713 prevents delayed neuronal death in the gerbil hippocampus. Tanaka, K., Mizukawa, K., Ogawa, N., Mori, A. Neurochem. Res. (1995) [Pubmed]
  14. Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease. Potkin, S.G., Anand, R., Fleming, K., Alva, G., Keator, D., Carreon, D., Messina, J., Wu, J.C., Hartman, R., Fallon, J.H. Int. J. Neuropsychopharmacol. (2001) [Pubmed]
  15. Effect of donepezil hydrochloride (E2020) on basal concentration of extracellular acetylcholine in the hippocampus of rats. Kosasa, T., Kuriya, Y., Matsui, K., Yamanishi, Y. Eur. J. Pharmacol. (1999) [Pubmed]
  16. The effect of acetylcholinesterase inhibitor (SDZ ENA 713) for r-CBF and focal cerebral ischaemia. Tsujimoto, S., Sakaki, T., Morimoto, T., Tominaga, M. Acta neurochirurgica. (1993) [Pubmed]
  17. An open-label study to evaluate the safety, tolerability and efficacy of rivastigmine in patients with mild to moderate probable Alzheimer's disease in the community setting. Bilikiewicz, A., Opala, G., Podemski, R., Puzyński, S., Łapin, J., Sołtys, K., Ochudło, S., Barcikowska, M., Pfeffer, A., Bilińska, M., Paradowski, B., Parnowski, T., Gabryelewicz, T. Med. Sci. Monit. (2002) [Pubmed]
  18. Rivastigmine for Alzheimer's disease. Birks, J., Iakovidou, V., Tsolaki, M. Cochrane database of systematic reviews (Online) (2000) [Pubmed]
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