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

The effects of monocrotophos and its newly synthesized analogues, RPR-II and RPR-V, on hematology and blood chemistry 24 hr post-treatment were studied in rats given doses of 0.96, 1.23, and 3.0 mg/kg po, respectively. It was found that monocrotophos caused a significant increase in the mean WBC count. RPR-V, a significant decrease in hematocrit and RBC count, whereas RPR-II did not alter any hematological parameter. The activities of membrane-bound enzymes in serum were not significantly changed by all three compounds except for a statistically significant increase of 38% in SGOT activity by RPR-II. Only monocrotophos caused a significant inhibition of the brain acetylcholinesterase activity. In vitro studies with partially purified preparations of rat brain cholinesterase revealed that monocrotophos was the most potent anticholinesterase agent, followed by RPR-II and RPR-V. All three compounds caused inhibition of rat brain cholinesterase by decreasing the Vmax and increasing the Km values, indicating a mixed type of inhibition. The two analogues appeared to be less neurotoxic than monocrotophos.
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PMID:A comparative study of blood changes and brain acetylcholinesterase inhibition by monocrotophos and its analogues in rats. 186 85

The effect of a new phosphorothionate, the ethyl ester of 2-butenoic acid 3-diethoxy phosphinothioyl (RPR-V) synthesized at the Indian Institute of Chemical Technology, Hyderabad was studied using peroral doses of 0.033, 0.066 and 0.099 mg kg(-1) in male and female rats daily over 90 days. This repeated administration of RPR-V caused significant inhibition of acetylcholinesterase, Na+-K+, Mg2+ and Ca2+-ATPases in the brain of male and female rats when measured after 45 and 90 days of treatment. The effects of the low dose were generally not statistically significant, whereas medium and high doses caused significant effects. Females were more susceptible with regard to brain AChE, but the reverse was seen with Mg2+-ATPase, suggesting sexual dimorphism. Enzyme recoveries were seen 28 days after the final dose. Since RPR-V not only inhibited AChE but also ATPases, it is possible that both synaptic transmission and nerve conduction were affected.
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PMID:Effects of a new phosphorothionate (RPR-V) on ATPases and acetylcholinesterase in rat brain by subchronic dosing. 933 39

This study was conducted to investigate the effect of a new phosphorothionate, the methyl ester of 2-butenoic acid-3-diethoxy phosphinothioyl (RPR-II) on membrane bound target enzymes aspartate amino transferase (ASAT), alanine amino transferase (ALAT) and RBC acetylcholinesterase (AChE) in different tissues of male and female albino wistar rats when treated orally with 0.014 (low), 0.028 (medium) and 0.042 (high) mg/kg daily for a period of 90 days. Repeated administration of RPR-II caused significant increase of ASAT and ALAT enzymes in serum, liver and kidney and significant decrease was recorded in lung in both male and female rats when measured after 45 and 90 days of treatment. This compound also caused significant inhibition of RBC AChE indicating its effect on nerve synapsis. Females were more susceptible than males with regard to ASAT and ALAT levels in serum and liver and also in kidney ASAT, whereas reverse trend was recorded in lung ALAT, suggesting sexual dimorphism in the treated rats. These studies also indicated that the levels of these affected enzymes were recovered to normal conditions after 28 days of post treatment (withdrawal study). Positive correlation was observed with regard to these enzymes between serum, liver and kidney, whereas in case of serum and lung a negative correlation was recorded. These enzymes profile elucidates lung necrosis whereas in other tissues the level of enzymes increased showing an adaptive mechanism due to the chemical stress.
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PMID:Biochemical alterations induced by a new phosphorothionate (RPR-II) in tissues of male and female rats. 1064 Nov 86

A novel phosphorothionate (2-butenoic acid-3-(diethoxy phosphinothioyl)-methyl ester (RPR-II), synthesized at the Indian Institute of Chemical Technology, Hyderabad, targets its effect on rat brain acetylcholinesterase (AChE) and Na(+)-K(+), Mg(2+), and Ca(2+) ATPases, as evident in this investigation. Three subchronic doses 0.014 (low), 0.028 (medium), and 0.042 (high) mg kg(-1) were administered to rats daily for a period of 90 days RPR-II caused statistically significant dose- and time-dependent inhibition in brain AChE and also in Na(+)-K(+), Mg(2+), and Ca(2+) ATPases in both male and female rats after 45 and 90 days of treatment. The low dose was generally insignificant while the medium and high doses were significantly effective. Females were more susceptible than males with regard to brain AChE, Na(+)-K(+), and Mg(2+) ATPases, which indicates sexual dimorphism in the treated rats. Interestingly, after 28 days post-treatment, recovery of these enzymes was observed. The relative sensitivities of these enzymes indicated that brain AChE was more sensitive than any of the ATPases, but among the ATPases Na(+)-K(+) ATPase was more susceptible than Ca(2+) or Mg(2+) ATPases. This compound, besides inhibiting the target of organophosphates, AChE, also inhibited different ATPases, suggesting both synaptic transmission and nerve conduction were affected.
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PMID:Inhibition of acetylcholinesterase and different ATPases by a novel phosphorothionate (RPR-II) in rat brain. 1102 90

Acute toxicity of monocrotophos (MCP) and its newly synthesized thiol analogs 2-butenoic acid-3-(diethoxyphosphinothionyl) methyl ester (RPR II) and 2-butenoic acid-3-(diethoxyphosphinothionyl) ethyl ester (RPR-V) was studied on euryhaline fish, Oreochromis mossambicus. The median lethal concentrations of MCP, RPR-II, and RPR-V are 11.506, 0.167, and 0.174 mgL(-1), respectively. Both the analogs were found to be 65-fold more toxic than MCP. Inhibitory and recovery patterns of brain, gill, and muscle acetylcholinesterase (AChE) was studied in vivo after exposure to LC(50) (96 h) concentrations. Recovery study was performed of regular intervals of day-1, -7, -14, -21, and -28 to establish the time course of 50% and 100% recovery in neurotransmitter enzyme of brain, gill, and muscle tissues. The sensitivity of the tissue AChE was in the order gill>brain>muscle. The relative toxicity of these compounds with regard to AChE was RPR-II>RPR-V>MCP. The MCP-treated fishes recovered at a faster rate than for RPR-V, followed by RPR-II.
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PMID:Effects of monocrotophos and its analogs in acetylcholinesterase activity's inhibition and its pattern of recovery on euryhaline fish, Oreochromis mossambicus. 1532 78