Discontinuation syndrome is a cluster of symptoms that appear when a patient terminates long-term medication. We report 2 patients with Alzheimer's disease who developed significant behavioral disturbances after the cessation of cholinesterase inhibitors. Although the clinical profile of discontinuation syndrome in cholinesterase inhibitors are yet poorly defined, it may be of importance to consider this syndrome when patients develop significant behavioral disturbances after these agents are stopped, and if more severe reactions are expected, retrial of these agents may be prudent.
Alzheimer Disease ; Cholinesterase Inhibitors* ; Cholinesterases* ; Humans

Activity-guided isolation of Heracleum moellendorffii roots led to four coumarin derivatives as acetylcholinesterase inhibitors. The structures of these isolates were characterized by spectroscopic method to be angelicin (1), isobergapten (2), pimpinellin (3), and (3S, 4R)-3, 4-epoxypimpinellin (4). All the isolated compounds 1, 2, 3, and 4 showed moderate inhibition activities against acetylcholinesterase with the IC₅₀ values of 10.2, 18.1, 21.5 and 22.9 µM, respectively. (3S, 4R)-3, 4-Epoxypimpinellin (4) was newly isolated from the plant source.
Acetylcholinesterase ; Cholinesterase Inhibitors ; Coumarins ; Heracleum* ; Methods ; Plants

Fourteen compounds were isolated from the stem of Angelica polymorpha. On the basis of spectral data, these compounds were identified as isoimperatorin (1), phellopterin (2), bergapten (3), xanthyletin (4), cnidilin (5), geijerine (6), (−)-3'-acetyl hamaudol (7), 7-demethylsuberosine (8), dehydrogeijerin (9), (−)-hamaudol (10), (+)-visamminol (11), divaricatol (12), scopoletin (13), and decursidate (14), respectively. Among them, compounds 4 - 6, 8, 9, 13, and 14 were isolated for the first time from A. polymorpha. Dehydrogeijerin (6) and geijerin (9) were isolated for the first time from genus Angelica. All isolates tested for inhibitory activity against acetylcholinesterae. Compounds 1 to 13 showed acetylcholinesterase inhibitory activity with IC₅₀ values ranging from 1.4 to 37.5 µM.
Acetylcholinesterase* ; Angelica* ; Cholinesterase Inhibitors* ; Chromones ; Coumarins ; Scopoletin

A total of 127 strains of endophytic fungi were isolated from roots, branches and leaves of Huperzia serrata. These strains were identified into 19 genera based on morphological characters and ribosomal DNA (rDNA) sequence analysis, there into Penicillium, Aspergillus and Podospora were dominant populations in H. serrata. From analysis results we found some endophytic fungi showed a certain degree of tissue preference. The isolation rate and colonization rate of stems were both larger than those of leaf and roots. After testing the acetylcholinesterase (AChE) inhibitory activity of these endophytic fungi, a total of 39 endophytic fungi belonging to 15 genera showed AChE inhibition. Eleven endophytic fungi showed potent AChE inhibition, 7 of which were isolated from leaf. The research not only provided theoretical basis for developing and utilizing the resources of endophytic fungi in H. serrata but also showed a new path for searching medicines resource which has AChE inhibitory activity.
Cholinesterase Inhibitors ; pharmacology ; Fungi ; classification ; isolation & purification ; Huperzia ; microbiology

Ophthalmoplegia following snake bite is a rare but not serious neurotoxic complication. However, symptoms like diplopia, blurred vision, and ocular discomfort can be emotionally devastating for a patient. We experienced one case f ophthalmoplegia following a snake bite. The patient complained of diplopia and ptosis that had developed several hours after the snake bite. The symptoms were completely resolved after pyridostigmine medication with antivenin treatment.
Cholinesterase Inhibitors ; Diplopia ; Humans ; Ophthalmoplegia* ; Pyridostigmine Bromide ; Snake Bites* ; Snakes*

No abstract available.
Cholinesterase Inhibitors ; Oculomotor Nerve Diseases* ; Oculomotor Nerve* ; Snake Bites* ; Snakes*

The success of accelerating the onset of neuromvacular blocking drugs by giving them in divided doses encouraged others to attempt the same "priming principle" using reversal agents. Naguib et al and Abdulatif et al demonstrated that the reversal time(time to reach a TOF of 0.75) was reduced when the reversal agent was administered in divided doses at T, 10% of control. But Donati et al and Szalados et al either could not detect any differences in the rate of reversal when anticholinestereses were administered in divided doses. This study hes been conducted to evaluate the reversal effects of neostigmine or pyridostigmine with priming principle in the rabbit after pancuronium injection when pro- found relaxation(PTC=0) was confirmed. Rabbits(n=60) were randomly allocated to 4 groups. After pancuranium 0.2mg/kg IV, the onset and recovery times were evalusted. When the profound relaxation(PTC=0) was confirmed at Smin. after pancuronium injection, neostigmine 50 ug/kg and atropine sulfate (atropine) 20 ug/kg were injected in group 1. At thst time, neostigmine 10/kg and atropine 4 ug/kg were injected and after 3min. neostigmine 40/kg and atropine 16 ug/kg were injected in group 2. At that time, pyridostigmine 250 ug/kg and atropine 20 ug/kg were injected in group 3. At that time, pyridostigmine 50 ug/kg and atropine 4 ug/kg were injected and after 3min. pyridostigmine 200 ug/kg and atropine 16 ug/kg were injected in group 4. The results were as follows :. 1) The time until 75% recovery of twitch amplitude was 53.1+/-12.4min. in group 1, 44.9+/-212.1min. in group 2, 54.9+/-9.7min. in group 3 and 48.2+/-7.1min. in group 4. The reversal times were tended to reduce when the reversal agents were administered with "priming principle" at the profound relaxation. 2) At the profound relaxation the reversal effects of neostigmine were greater than that of pyridostigmine.
Atropine ; Cholinesterase Inhibitors* ; Muscle Relaxation* ; Neostigmine ; Pancuronium ; Pyridostigmine Bromide ; Relaxation

Alzheimer's disease (AD) is associated with cognitive and functional impairment as well as neuropsychiatric complications, including psychotic symptoms such as delusions and hallucinations. Recent studies strongly suggest that delusions should be separated from hallucinations. While AD with delusions is a phenotypically distinct from AD without delusions, subtypes of delusions may also define further distinct clinical entities. There has been also considerable debate as to whether delusions in patients with AD differ etiologically, phenomenologically, and therapeutically from delusions in other primary psychiatric illnesses. In other words, whether they are caused by changes to key areas of the brain that have been linked to the presence of delusions. This has led to speculation that these symptoms may respond better to certain drugs such as cholinesterase inhibitors. Integrating the epidemiology, clinical phenomenology, neuropathological and genetic literature for delusions in AD allows us to speculate on pathophysiology and is essential to making progress in the area of delusions in AD.
Alzheimer Disease* ; Brain ; Cholinesterase Inhibitors ; Delusions* ; Epidemiology ; Hallucinations ; Humans

Multi-target drugs attract increasing attentions for the therapy of complicated neurodegenerative diseases. In this study, a computer-assisted strategy was applied to search for multi-target compounds by the pharmacophore matching. This strategy has been successfully used to design dual-target inhibitor models against both the acetylcholinesterase (AChE) and poly (ADP-ribose) polymerase-1 (PARP-1). Based on two pharmacophore models matching and physicochemical properties filtering, one hit was identified which could inhibit AChE with IC50 value of (0.337 +/- 0.052) micromol x L(-1) and PARP-1 by 24.6% at 1 micromol x L(-1).
Acetylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; pharmacology ; Computer-Aided Design ; Drug Discovery ; methods ; Poly(ADP-ribose) Polymerase Inhibitors

OBJECTIVETo screen the peptide inhibitor of acetylcholinesterase (AChE) from 12-mer random phage display peptide library.

METHODSHuman AChE was used as the target to screen its binding peptides from 12-mer random phage display peptide library. The positive phage clones were isolated after three rounds of biopanning followed then by sequence analysis and their activity evaluation.

RESULTSSix positive phage clones binding to human AChE were obtained, and 4 of them sharing the conservative sequence W(S/P)HY inhibited the enzyme activity of AChE.

CONCLUSIONAcquisition of AChE inhibitor from phage display library provides clues for designing peptide inhibitors of AChE.

Acetylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; metabolism ; pharmacology ; Humans ; Peptide Library ; Peptides ; metabolism ; pharmacology ; Protein Binding