Butyrylcholinesterase decreased

The dual inhibition of acetylcholinesterase and butyrylcholinesterase may lead to broader efficacy. As acetylcholinesterase activity decreases with disease progression, the acetylcholinesterase-selective agents may lose their effect, while the dual inhibitors may still be effective due to the added inhibition of butyrylcholinesterase. However, this has not been demonstrated clinically. 

Consistent decreases in plasma cholinesterase may not have been observed in rats and dogs because they were treated with lower doses of diisopropyl methylphosphonate. In general, depression of plasma cholinesterase, also known as pseudocholinesterase or butyrylcholinesterase, is considered a marker of exposure rather than an adverse effect. Depression of cholinesterase activity in red blood cells (acetylcholinesterase) is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity. It is considered an adverse effect. Acetylcholinesterase is found mainly in nervous tissue and erythrocytes. Diisopropyl methylphosphonate was not found to inhibit RBC... 

Although this study (Hart 1980) did not identify an effect level, the NOAEL is below the LOEL found in all studies examining the toxicity of diisopropyl methylphosphonate. The LOEL for diisopropyl methylphosphonate is 262 mg/kg/day for male mink and 330 mg/kg/day for female mink (Bucci et al. 1997), doses at which statistically significant decreases in plasma cholinesterase (butyrylcholinesterase) but not RBC cholinesterase (acetylcholinesterase) activity were observed (Bucci et al. 1997). In general, a decrease in plasma cholinesterase activity is considered to be a marker of exposure rather than a marker of adverse effect, while a decrease in RBC acetylcholinesterase activity is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity and is thus considered an adverse effect. Diisopropyl methylphosphonate was not found to inhibit red blood cell cholinesterase at doses at which plasma cholinesterase was significantly inhibited. No effects were observed in males at 45 mg/kg/day (Bucci et al. 1997) or at 63 mg/kg/day (Bucci et al. 1994), and no effects were observed in females at 82 mg/kg/day (Bucci et al. 1994), or at 57 mg/kg/day (Bucci et al. 1997). 

Most of the pesticide biosensors are designed based on the inhibitory property of enzymes. AChE and butyrylcholinesterase (BChE) are widely used in the development of pesticide biosensors [17, 18], Inhibition leads to a decrease in activity, which... 

Butyrylcholinesterase (BuChE EC 3.1.1.8) from either horse or mice serum displayed different profiles. A steady state was not developed, although the rate constants of inhibition decreased with time. Since the presence of multiforms of serum BuChE has been established, it is likely that the first-order plot represents more than one exponent. The inhibited enzyme did not regenerate as fast as AChE-TDPI conjugate. However, 2-PAM enhanced the reactivation of horse-serum BuChE after inhibition with TDPI. The various rate constants were computed from the initial slopes of the inhibition and reactivation of... 

Oxazocine 119 is a synthetic derivative of galanthamine 162. The latter is a tertiary alkaloid, isolated from amaryllidaceae, which is a central acting competitive and reversible inhibitor of acetylcholinesterase that enhances cognitive functions in Alzheimer s patients. However, oxazocine 119 showed a decreased potency as an acetylcholinesterase inhibitor and a marked selectivity with respect to butyrylcholinesterase, probably because butyrylcholinesterase accommodates steric bulk around the catalytic site, better than acetylcholinesterase <2003BML2389>. 

Tacrine, an aminoacridine synthesized in the 1930s, is a nonclassic cholinesterase inhibitor that binds to both AChE or butyrylcholinesterase (46). It was approved in 1993 for the treatment of AD. Approximately 20% of tacrine-treated patients may show improvement, but its use has been limited because of hepatotoxicity. Use of tacrine has greatly decreased because of the recent development of safer AChEls. Tacrine is extensively metabolized by CYP450 to at least three metabolites. The major metabolite, 1-hydroxy-tacrihe, is active. Its elimination half-life is between 1.5 and 4 hours, with metabolites being are excreted via the urine. 

Documented effects The alkaloid protopine (fumarine) caused narcosis in amphibians and, in mammals, caused paralysis of sensory nerve endings and increased reflex excitability. The alkaloid slightly increased the effects of analeptics and induced catalepsy (Chen-Gu 1957 Cheney 1963). In acute experiments with animals under narcosis, reduced heart rate and increased heartbeat amplitude occurred and, for a short time, decreased blood pressure was observed. Protopine has antiarrhythmic action with better effects than novocainamide and quinidine (Sadritdinov and Kurmukov 1980). In a screen to determine effects on platelet aggregation, extracts of this species showed complete inhibition of aggregation. This result was found to be caused by protopine (Sener 1994). Extracts of the dried plant displayed high rates of inhibition against the enzymes acetylcholinesterase and butyrylcholinesterase, which are associated with Alzheimer s disease (Orhan et al. 2004). 

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