Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present work addresses the effects of three antineoplastic drugs [cyclophosphamide (CP), cisplatin (CDDP) and methotrexate (MTX) which are in current use for the treatment of various tumors] on turnover kinetics of human erythrocyte membrane-bound acetylcholinesterase (AcChoEase, EC 3.1.1.7). It was found that CP and MTX significantly decreased kcat and ksp, whereas CDDP decreased only the kcat value, (ksp was non-significantly affected). In light of these findings, the CP, CDDP and MTX needs particular attention in tumor therapy and their effects on turnover number must be considered at the time of administering these drugs to cancer patients.
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PMID:Investigation of the effect of anti-neoplastic drugs, cyclophosphamide, cisplatin and methotrexate on the turnover kinetics of human erythrocyte acetylcholinesterase. 879 56

The aim of this prospective study was to evaluate if there was a statistical correlation between allogeneic blood transfusion and postoperative infections, and if this could have a dose-dependent pattern. The evaluation was based on multiple logistic and receiver operating characteristics (ROC) curve analyses. On hospital admission the following parameters were determined in 267 consecutive patients with colorectal cancer: hemoglobin, serum albumin, serum cholinesterase activity, total iron binding capacity and weight loss. Duration of operation, operative blood loss, amount of transfused blood, Dukes' cancer stage and occurrence of postoperative infections were also recorded. One hundred and thirty-two patients (49.4%) were given perioperatively allogeneic blood. Postoperative infections developed in 47 (17.6%) patients. Multivariate analysis identified allogeneic blood transfusion as the only variable related to the occurrence of postoperative infections (p < 0.05). ROC curve analysis showed that the risk for the occurrence of infection was significantly higher in patients transfused one unit of blood (p < 0.01). Moreover, a significant trend between increasing number of transfused blood units and susceptibility to infection was found (p < 0.00019).
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PMID:A single unit of transfused allogeneic blood increases postoperative infections. 891 60

The present work addresses the 'dual temperature' model for the estimation of Gibb's free energy change (delta G), enthalpy change (delta H), heat of activation (delta H.) entropy change (delta S), temperature coefficient (Q 10) and activation energy (Ea) of chicken brain acetylcholinesterase (AChE) inhibited by cyclophosphamide monohydrate (CP). In this investigation, the PZ factor (number of sterically and energy wise favorable collisions occurring between CP and AChE) has also been studied. The inhibitor has considerably increased all energetics parameters except delta S and Q10. These results are in general agreement with the data from the other reported studies. The significance of the use of CP in cancer therapy and various aspects of thermodynamic parameters have also been discussed.
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PMID:Dual temperature model for the estimation of energetics parameters for acetylcholinesterase inhibition by cyclophosphamide. 935 76

The inhibitory effect of cisplatin (CDDP) on camel retina acetylcholinesterase (AChE) was characterized. The CDDP effect was independent of the time of incubation with AChE before the addition of substrate, indicative of reversible inhibition. Moreover, dilution data prove that CDDP is a reversible inhibitor of camel retina AChE. Cisplatin inhibited AChE activity of camel retina in a concentration- and time-dependent manner, the IC50 values being 5.32 and 0.196 mM at 5 min and 24 h incubation times, respectively. The IC50 has dual components, i.e. directly proportional and inversely proportional to 0-1.5 h and 1.5-24 h incubation periods, respectively. The Michaelis-Menten constant (Km) for the hydrolysis of acetylthiocholine iodide (ASCh) was found to be 0.0796 mM and Vmax was 0.668 micromol/min/mg protein. Kmapp and Vmaxapp both decreased as the CDDP concentration increased. Dixon as well as Lineweaver-Burk plots and their secondary replots indicated that the nature of the inhibition was of the pure uncompetitive type. The value of Ki was estimated as 0.811 mM by the primary and secondary replots of the Lineweaver-Burk and Dixon plots. Kiapp decreased while Vmaxiapp increased after increasing the ASCh concentration.
Cancer Lett 1998 Jun 05
PMID:Kinetics of the inhibition of acetylcholinesterase in camel retina by cisplatin. 965 96

Irinotecan (CPT-11 [Camptosar]) is an important new chemotherapeutic drug that demonstrates activity against a broad spectrum of malignancies, including carcinomas of the colon, stomach, and lung. Unfortunately, frequent and often severe gastrointestinal toxicities, particularly diarrhea, have limited its more widespread use. A cholinergic syndrome resulting from the inhibition of acetylcholinesterase activity by irinotecan is frequently seen within the first 24 hours after irinotecan administration but is easily controlled with atropine. Late diarrhea occurs in the majority of patients, however, and is National Cancer Institute (NCI) grade 3 or 4 in up to 40%. The late syndrome appears to be related to the effects on the bowel of SN-38, the active metabolite of irinotecan, which undergoes biliary excretion and inactivation. Early recognition and treatment of late diarrhea with high-dose loperamide have reduced, although not entirely eliminated, patient morbidity. Further study is needed to identify the mechanism of irinotecan-induced late diarrhea and to evaluate potential new therapies.
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PMID:Gastrointestinal toxicity or irinotecan. 972 96

The practical pharmacological approaches currently available to palliate the cognitive and functional losses in early Alzheimer's disease (AD) include cholinesterase inhibitors (ChEI), antioxidants (e.g., vitamin E), anti-inflammatory agents, estrogen, seligiline, vasoactive agents, and ginkgo biloba. Reviewing available data on these therapies and using models from medical illnesses such as cancer and hypertension, we highlight the urgent need for evaluating combination therapies in early AD.
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PMID:Combination therapy for early Alzheimer's disease: what are we waiting for? 977 22

Patients treated with high doses of CPT-11 rapidly develop a cholinergic syndrome that can be alleviated by atropine. Although CPT-11 was not a substrate for acetylcholinesterase (AcChE), in vitro assays confirmed that CPT-11 inhibited both human and electric eel AcChE with apparent K(i)s of 415 and 194 nM, respectively. In contrast, human or equine butyryl-cholinesterase (BuChE) converted CPT-11 to SN-38 with K(m)s of 42.4 and 44.2 microM for the human and horse BuChE, respectively. Modeling of CPT-11 within the predicted active site of AcChE and BuChE corroborated experimental results indicating that, although the drug was oriented correctly for activation, the constraints dictated by the active site gorge were such that CPT-11 would be unlikely to be activated by AcChE.
Cancer Res 1999 Apr 01
PMID:The anticancer prodrug CPT-11 is a potent inhibitor of acetylcholinesterase but is rapidly catalyzed to SN-38 by butyrylcholinesterase. 1019 14

The present work addresses the analyses of some novel kinetic parameters (k(t), K(v), t50, K(ir), t(c), m(c), IC50, IC99 and Ki) of human erythrocyte membrane-bound acetylcholinesterase (AChE, EC 3.1.1.7) inhibition by cis-diamminediaquaplatinum II (PDC). PDC is under a clinical trial for use as an antineoplastic drug. The authors recently reported that PDC and cisplatin have the ability to inhibit AChE activity in vitro. Therefore this study was designed to determine the estimation of time constant (k(t)), velocity constant (K(v)), 50% inhibition time (t50), inhibition rate constant (K(ir)), transition concentration (t(c)), meeting concentration (m(c)), 50% inhibition (IC50), 99% inhibition (IC99) and inhibition constant (Ki) by novel methods. The details are described in the text.
Cancer Lett 1999 Apr 26
PMID:Human erythrocyte acetylcholinesterase inhibition by cis-diamminediaquaplatinum (II): a novel kinetic approach. 1037 82

Water-soluble 20(S)-glycinate esters of two highly potent 10,11-methylenedioxy analogues of camptothecin (CPT) have been synthesized and evaluated for their ability to eradicate human breast cancer tumor xenografts. The glycinate ester moiety increases the water solubility of the 10,11-methylenedioxy analogues 4-16-fold. However, in contrast to CPT-11, a water-soluble CPT analogue that was recently approved for second line treatment of colorectal cancer, the 20(S)-glycinate esters do not require carboxylesterase for conversion to their active forms. The glycinate esters are hydrolyzed to their parent, free 20(S)-hydroxyl active analogues in phosphate buffer (pH 7.5) and in mouse and human plasma. The glycinate esters are also 20-40-fold less potent than CPT-11 in inhibiting human acetylcholinesterase. In vivo, we examined 20(S)-glycinate-10,11-methylenedioxycamptothecin, 20(S)-glycinate-7-chloromethyl-10,11-methylenedioxycamptothecin, and CPT-11. We found that the two 10,11-methylenedioxy analogues had antitumor activity against breast cancer xenografts that was comparable to that of CPT-11. Our results indicate that water-soluble 20(S)-glycinate esters of highly potent CPT analogues provide compounds that maintain biological activity, do not require interactions with carboxylesterases, and do not inhibit human acetylcholinesterase.
Cancer Res 1999 Jul 15
PMID:Water soluble 20(S)-glycinate esters of 10,11-methylenedioxycamptothecins are highly active against human breast cancer xenografts. 1041 5

We report a case of Lambert-Eaton myasthenic syndrome (LEMS) associated with idiopathic thrombocytopenic purpura (ITP) and diffuse panbronchiolitis (DPB). An extensive search for malignancy yielded negative results. Interestingly, ITP and DPB developed simultaneously when the patient suffered from myasthenic symptoms. This is the first report in the Japanese or English literature of an association of LEMS, ITP, and DPB. The use of cholinesterase blocker alone did not improve the myasthenic symptoms, and the symptoms and signs relapsed with the tapering of prednisolone (PSL) dosage. However, after administration of immunoglobulin (IVIG) (0.4 g/kg/day x 5 days), low-dose PSL (20 mg/day) alleviated the LEMS and ITP, and the diseases have remained in remission for 8 months without additional IVIG. We suspect that there is a synergistic relationship between IVIG and PSL.
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PMID:Lambert-Eaton myasthenic syndrome associated with idiopathic thrombocytopenic purpura and diffuse panbronchiolitis: long-term remission after a course of intravenous immunoglobulin combined with low-dose prednisolone. 1055 1


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