Disease relevance of Trichlorphon

• Integration of schistosomiasis control into primary health care services in The Gambia required semiliterate health workers to administer praziquantel and metrifonate to the community in doses based on weight [1].
• Environmental trichlorfon and cluster of congenital abnormalities [2].
• We have investigated the acute and chronic effect of metrifonate (MTF) and dichlorvos (DDVP), respectively the prodrug and active acetylcholinesterase inhibitor, on the secretory processing of the amyloid precursor protein (APP) in SH-SY5Y neuroblastoma cells [3].
• They suggest that APOE genotypes do not necessarily predict an AD patient's response to metrifonate treatment and that APOE genotype may not influence the rate of disease progression for patients with mild to moderate AD [4].
• Trichlorfon (metrifonate) was given intermittently to 37 schoolboys with urinary schistosomiasis living in a hyperendemic area of the Sudan. Patients were followed up for three years [5].

Psychiatry related information on Trichlorphon

• Metrifonate for Alzheimer's disease: is the next cholinesterase inhibitor better [6]?
• The complete Koro complex in an elderly male Briton was associated with psychotic depression following a non-dominant temporoparietal stroke [7].
• The metrifonate treatment did not affect cognitive testing parameters but reduced swimming speed and locomotor activity in both genotypes [8].
• Experiments conducted on pregnant Wistar rats show that chlorophos (Dipterex) has embroyotoxic and teratogenic effects after oral introduction in a 80 mg/kg dose during a critical period of embryogenesis [9].
• The study compared the efficacy of acute versus chronic metrifonate treatment to improve initial and reversal learning of the water maze spatial navigation task in medial septal-lesioned rats [10].

High impact information on Trichlorphon

• At gastrula stage Sp88 transcripts are almost completely confined to the nucleus [Lev, Z., Thomas, T. L., Lee, A. S., Angerer, R. C., Britten, R. J. & Davidson, E. H. (1980) Dev. Biol, 75, in press] [11].
• Metrifonate increases neuronal excitability in CA1 pyramidal neurons from both young and aging rabbit hippocampus [12].
• We have also followed APP expression and metabolism after long-term treatment with metrifonate [3].
• CONCLUSIONS: The findings from these studies of up to 26 weeks' duration do not clearly support an interaction between APOE genotype and metrifonate treatment effects [4].
• The interaction of APOE genotype with the metrifonate effect on global function also was not significant (p = 0.70) [4].

Chemical compound and disease context of Trichlorphon

• The present study investigated the dose-response characteristics of donepezil, tacrine, rivastigmine and metrifonate in inducing tremor, lacrimation, salivation and hypothermia and the duration of action of these compounds in Lister hooded rats [13].
• Further trials of mebendazole and metrifonate in the treatment of onchocerciasis [14].
• In order to examine the effect of metrifonate, 156 patients with mixed Schistosoma haematobium and mansoni infection were randomly divided into three groups and treated with metrifonate (twice 10 mg/kg body weight), oxamniquine (60 mg/kg) and praziquantel (40 mg/kg), respectively [15].
• Malumfashi Endemic Diseases Research Project, V. Concurrent single dose metrifonate and niridazole in urinary schistosomiasis [16].
• In a single-blind comparative study of diethylcarbamazine (DEC) and metrifonate against onchocerciasis, 20 patient received a total dose of 6.6 g DEC over a two-week period and 20 patients each received one dose of metrifonate 10 mg/kg body weight at ten-day intervals, three times [17].

Biological context of Trichlorphon

• In contrast, the methylhalides, trichlorfon and MAM all methylate DNA and inhibit O6-guanine-DNA methyltransferase (OGMT), an important DNA repair enzyme [18].
• Quantification of infection with Schistosoma haematobium in relation to epidemiology and selective population chemotherapy. II. Mass treatment with a single oral dose of metrifonate [19].
• The structural development of fetuses was altered when Dipterex was administered by diet to pregnant rats from days 6 through 15 of gestation [20].
• By causing spindle aberrations and influencing chromosome congression, trichlorfon appears, therefore, to predispose mammalian oocytes to random chromosome segregation, especially when they undergo a first division and develop to metaphase II during exposure [21].
• However, formation of a spindle was disturbed in many oocytes resuming meiosis I in the presence of trichlorfon [21].

Anatomical context of Trichlorphon

• Trichlorfon exposure, spindle aberrations and nondisjunction in mammalian oocytes [21].
• The effects of chronic (5 week) metrifonate treatment on the blood-brain barrier of the adult rat were examined [22].
• Metrifonate treatment resulted in steady-state, dose-dependent acetylcholinesterase (AChE) inhibition in red blood cells [23].
• Sustained effect of metrifonate on cerebral glucose metabolism after immunolesion of basal forebrain cholinergic neurons in rats [24].
• A study of the aneugenic activity of trichlorfon detected by centromere-specific probes in human lymphoblastoid cell lines [25].

Associations of Trichlorphon with other chemical compounds

• These data indicate that chronic metrifonate treatment may increase the extracellular acetylcholine level via cholinesterase inhibition, but it does not have any effects on the blood-brain barrier [22].
• OBJECTIVE: We investigated the memory-enhancing effects of the PDE5 inhibitor sildenafil and AChE inhibitors metrifonate and donepezil in the object recognition task to find out whether acquisition or consolidation processes were affected by these drugs [26].
• There were no statistically significant differences in primary pharmacokinetic parameters--Cmax, t(max), area under the concentration-time curve (AUC), and t1/2--of metrifonate and dichlorvos among the different groups [27].
• Effect of subchronic treatment with metrifonate and tacrine on brain cholinergic function in aged F344 rats [28].
• Also, the combination of nimodipine 3 or 10 mg/kg and a subthreshold dose of metrifonate 10 mg/kg could not suppress high-voltage spindles or scopolamine treatment-induced spectral EEG activity abnormalities [29].

Gene context of Trichlorphon

• The effects of long-term treatment with metrifonate, a cholinesterase inhibitor, on cholinergic activity, amyloid pathology, and cognitive function in APP and PS1 doubly transgenic mice [8].
• In addition, treatment with the AChE-inhibitor metrifonate improved performance in an olfactory-learning assay [30].
• Metrifonate was found to inhibit BChE more than AChE [31].
• Following single metrifonate administration little inhibition of AChE was observed [32].
• Moreover, chronic metrifonate treatment did not have any effect on the distribution of the acetylcholinesterase molecular forms [22].

Analytical, diagnostic and therapeutic context of Trichlorphon

• A case-control study and environmental investigations pointed the finger of suspicion at the excessive use of trichlorfon at local fish farms [2].
• Bath perfusion of metrifonate (10-200 microM) dose-dependently decreased both postburst afterhyperpolarization (AHP) and spike frequency adaptation (accommodation) in neurons from young and aging rabbits (AHP: p < 0.002, young; p < 0.050, aging; accommodation: p < 0.024, young; p < 0.001, aging) [12].
• The conditions (sensitive period and doses) for producing hypoplasia in guinea-pig offspring after treatment of pregnant guinea-pigs with the organophosphorous agent trichlorfon (metrifonate, 0,0-dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate) were examined [33].
• We recorded from visually identified CA1 hippocampal pyramidal neurons in vitro using whole cell voltage-clamp technique to better isolate and characterize which component currents of the AHP are affected by metrifonate [34].
• An indirect cholinesterase inhibitor, metrifonate, increases neocortical EEG arousal in rats [35].

References