Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Young adult male and female Wistar rats were inhalationally exposed head-only for 1 or 4 h to different anticholinesterase aerosols. The compounds tested were dichlorvos, fenamiphos, methamidophos, parathion, a pyrimidine thiophosphate and the carbamate propoxur. These compounds are direct or indirect inhibitors of cholinesterase activity. Immediately after termination of exposure to the compounds, the rats were anesthetized with barbiturate and subjected to pulmonary function tests. An acetylcholine provocation test was performed to correlate the effect of the cholinesterase inhibition and lung resistance. The results basically revealed that by inhalation exposure bronchoconstriction in the absence of acetylcholine provocation did not occur at toxicologically significant doses of the pesticides. An increase in lung resistance was observed only after provocation. However, measurements of plasma cholinesterase activity proved to be more sensitive than the provocation test. With regard to their diagnostic value, the results of the reported study may be summarized as follows (beginning with the most sensitive parameter): plasma cholinesterase activity depression greater than or equal to acetylcholine-induced bronchoconstriction greater than or equal to cholinergic symptoms greater than erythrocyte cholinesterase activity depression greater than pulmonary resistance without acetylcholine provocation.
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PMID:Effects of inhaled cholinesterase inhibitors on bronchial tonus and on plasma and erythrocyte acetylcholine esterase activity in rats. 367 30

The hypothesis that the toxic effects of imidocarb mediated by reduced cholinesterase activity might be intensified by hypomagnesaemia was tested in calves. Hypomagnesaemia was induced in 12 males (50 kg) using an artificial milk based on a commercial nondairy coffee creamer. Although plasma magnesium levels reached 0.33 mmol litre-1 in two weeks no clinical signs were detected. In 12 control calves a daily magnesium supplement of 0.6 g was inadequate although the published requirement is 0.45 g; it was raised to 1.2 g to keep plasma magnesium normal. Lighter calves developed hypomagnesaemia more readily and fast-growing calves had lower plasma urea concentrations. Plasma calcium, but not plasma magnesium, showed significant positive correlation with plasma albumin. The only statistically significant effects of hypomagnesaemia were slight elevations of white cell count and plasma sodium. The hypomagnesaemic and normomagnesaemic calves were divided into two equal groups and treated with 3.3 mg kg-1 of imidocarb dipropionate or a placebo. The drug produced the expected clinical signs of mild toxicity and depression of cholinesterase but no other adverse effects. Transient slight depressions of plasma calcium and potassium concentration, a transient rise of plasma sodium and elevation of creatine kinase occurred. None of the effects of imidocarb treatment was intensified by hypomagnesaemia except, perhaps, constriction of the pupils; generally, hypomagnesaemic animals were affected less.
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PMID:Effect of induced hypomagnesaemia on the toxicity of imidocarb in calves. 370 46

The chronic effects of sublethal injections of the cholinesterase inhibitor, paraoxon, on transmitter release were examined in the rat. Rats were chronically treated daily with the organophosphate, paraoxon (0.3 mg/kg b.wt.), that is known to inhibit acetylcholinesterase irreversibly. Severe symptoms of intoxication were evident in animals during the first few days of treatment but by day 11 the symptoms disappeared despite continued treatment and depression in acetylcholinesterase. Intracellular recording techniques were used to determine if the observed behavioral changes to chronic treatment could be correlated with changes in neuromuscular transmission. Measurements of MEPPs demonstrated that tolerance could not be attributed to a decrease in postsynaptic sensitivity. Measurements of EPPs, quantal release and binomial statistical parameters demonstrated that tolerance can be correlated with presynaptic changes. Chronic treatment with paraoxon decreased transmitter release and this can be attributed to a decrease in the transmitter store and mobilization ability. It is suggested that the depression in quantal release at the neuromuscular junction and at cholinergic synapses could account for behavioral tolerance.
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PMID:Chronic effects of paraoxon on transmitter release and the synaptic contribution to tolerance. 371 75

Desoxypeganine hydrochloride isolated from Peganum harmala L. caused in animals a pronounced depression of cholinesterase activity. By anticholinesterase activity desoxypeganine was ten times superior peganine hydrochloride and 2 times galanthamine hydrochloride. In the experiments on anesthetized cats desoxypeganine hydrochloride eliminated blockade of neuromuscular conductivity induced by diplacine and on the contrary enhanced blockade induced by ditilin. It increases sensitivity to acetylcholine of the straight abdominal muscle of the frog and isolated segments of the small intestine. Desoxypeganine hydrochloride is used for treatment of patients with lesions of the peripheral nervous system.
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PMID:[Pharmacological characteristics of desoxypeganine hydrochloride]. 372 Sep 32

Clinical and pulmonary function changes induced by intravenous dichlorvos (2,2-dichlorvinyldimethyl phosphate) (DDVP) toxicosis, and reversibility of these changes after atropine treatment were investigated in six Friesian calves one to three months old. From one minute after dosage, all animals showed severe respiratory distress, excitation, weakness, muscle fasciculation and cholinesterase inhibition. Decrease in dynamic lung compliance and arterial oxygen tension and increase in total pulmonary resistance, viscous work of breathing and alveolar arterial oxygen gradient were highly significant (P less than 0.01). On the other hand, body secretions, heart rate, respiratory rate, tidal volume and arterial carbon dioxide tension were not significantly affected by DDVP injection. Atropine promptly and completely reversed these changes, except for muscle fasciculations, central depression and cholinesterase inhibition which disappeared progressively within 24 hours.
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PMID:Pulmonary function changes induced by experimental dichlorvos toxicosis in calves. 373 27

The pretreatment of calves with a single dose of 10 mg kg-1 dieldrin or 21 daily doses of 10 mg kg-1 phenobarbitone increased the toxicity of diazinon as reflected by the development of more severe clinical signs and greater depression in whole blood cholinesterase activity in the pretreated calves. Induction by dieldrin or phenobarbitone of the hepatic microsomal enzyme amidopyrine-N-demethylase was also accompanied by a concurrent rise in the liver carboxylesterase activity.
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PMID:Effect of pretreatment with hepatic microsomal enzyme inducers on the toxicity of diazinon in calves. 380 24

The changes in brain acetylcholinesterase (AChE), acid phosphatase (APase), and 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP), and plasma butyrylcholinesterase (BuChE) activities were investigated in hens treated with a single, dermal dose (100-1000 mg/kg) of S,S,S-tri-n-butyl phosphorotrithioate (DEF). Three control groups consisted of hens left untreated, given a single, dermal dose of 500 mg/kg tri-o-cresyl phosphate (TOCP, positive control for organophophorous compound-induced delayed neurotoxicity), or 10 mg/kg O,O-diethyl O-4-nitrophenyl phosphorothioate (parathion, negative control). Brain AChE activity, determined 28 days after application, was significantly inhibited in hens given 500-1,000 mg/kg DEF and in TOCP- and parathion-treated hens. In contrast, brain APase and CNP activities were significantly higher in all treatments as compared with those of the untreated hens. Parathion, however, caused the least increase in these enzymatic activities as compared to DEF or TOCP. A single, dermal dose of DEF or TOCP also caused an initial decrease in plasma BuChE activity with maximum depression of enzymatic activity observed 1 to 7 days after administration. This decrease was dose dependent and the enzymatic activity showed partial recovery with time. Hens treated with single, dermal doses of DEF, ranging from 250 to 1000 mg/kg, developed ataxia which progressed to paralysis in some hens. Histopathologic examination revealed axon and myelin degeneration of the spinal cord and peripheral nerves of some hens. The severity and frequency of the neuropathologic lesions were dose dependent. Neurologic dysfunctions and neuropathologic lesions seen in DEF-treated hens were similar to those exhibited in TOCP-treated hens. While parathion produced acute cholinergic effects, it did not cause delayed neurotoxicity. The changes in brain and plasma enzymes are discussed in relation to their role in the pathogenesis of DEF-induced delayed neurotoxicity.
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PMID:Brain acetylcholinesterase, acid phosphatase, and 2',3'-cyclic nucleotide-3'-phosphohydrolase and plasma butyrylcholinesterase activities in hens treated with a single dermal neurotoxic dose of S,S,S-tri-n-butyl phosphorotrithioate. 395 29

The disposition of [3H]diisopropylfluorophosphate (DFP) and its metabolites was studied in mice after iv treatment. In addition, disposition of [3H]DFP in selected tissues was correlated with cholinesterase activity and spontaneous activity following DFP treatment. Within 1 min of administration [3H]DFP had penetrated tissues and was already irreversibly bound. The tissue concentrations of [3H]DFP declined in a rapid fashion so that after 2 hr all concentrations were below 50 pg/mg tissue. The major portion of radioactivity was bound to tissue in the form of [3H]diisopropylphosphoric acid (DIP). There was a decline in [3H]DIP with time in all tissues except liver, kidneys, and fat, which reached a maximum at 30 min before declining. The only appreciable quantities of [3H]DIP remaining after 3 days were in liver and kidneys. There was also evidence that [3H]DFP was rapidly hydrolyzed to free [3H]DIP which was found in all tissues within 1 min of [3H]DFP administration. [3H]DIP concentrations were equivalent to or exceeded those of [3H]DFP in all tissues, except brain. Cholinesterase inhibition in plasma, diaphragm, and brain following DFP treatment (1 mg/kg, iv) was temporarily correlated with the concentrations of bound [3H]DIP in these same tissues between 1 hr and 3 days. Cholinesterase inhibition in brain and diaphragm did not correlate well with bound [3H]DIP at earlier time points which suggested the presence of noncholinesterase binding. DFP treatment (1 mg/kg) also induced motor hypoactivity which lasted up to 6 hr after iv injection. The time course of motor hypoactivity was not correlated with free [3H]DFP, bound [3H]DIP concentrations in the brain, or with cholinesterase inhibition in the brain, which suggested that noncholinesterase bound [3H]DIP was responsible for this CNS depression.
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PMID:Biodisposition of [3H]diisopropylfluorophosphate in mice. 397

Sub-acute exposure to anti-cholinesterase organophosphorous compounds induces, in humans, cognitive and emotional deficits which include depression, anxiety, emotional lability, and schizophrenic-like symptoms. Neuroleptic drugs used to treat similar clinical conditions bind to serotonergic (S2) and dopaminergic (D2) receptors, suggesting that these sites are involved in the psychiatric consequences of organophosphate exposure. Rats were given saline or soman (50 micrograms/kg, SC) on a sub-acute regimen (three times weekly for four weeks) and killed 1 hr, 1 day or 3 days after the final injection. Response of regional neuroleptic receptors to soman intoxication was assessed using 3H-spiperone as ligand. Initial high affinity binding experiments using mianserine, haloperidol, or both to identify specific cortical binding revealed that mianserine displaceable binding sites showed the greatest down-regulation in response to soman. Subsequent kinetic analyses of mianserine displaceable 3H-spiperone binding indicated a dramatic decrease in the number of hippocampal binding sites and a decrease in the affinity of cortical binding sites. These S2 sites, considered to be involved with neural excitation, have the ability to self-regulate and appear to be involved in the expression of soman neurotoxicity.
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PMID:Regional sensitivity of neuroleptic receptors to sub-acute soman intoxication. 399 58

The biodisposition of [3H]diisopropylfluorophosphate (DFP) and its metabolites was studied in mice after inhalation administration. In addition, the time course of DFP-induced cholinesterase inhibition in selected tissues, hypothermia, and motor coordination were studied to determine a possible correlation with [3H]DFP, or its metabolites. The time course of tissue concentrations of [3H]DFP showed that [3H]DFP rapidly penetrated all tissues and was quickly hydrolyzed to [3H]diisopropylphosphoric acid (free [3H]DIP) or was covalently bound to tissue (bound [3H]DIP). By 1 hr, the greater portion of the radioactivity was in the form of bound [3H]DIP. Cholinesterase inhibition in brain, lung, diaphragm, and plasma was temporally related to concentrations of bound [3H]DIP between 5 min and 1 day, except at early time points for the lung. Motor incoordination (rotarod test) produced by DFP exposure had a rapid onset, with complete recovery by 10 hr. DFP-induced hypothermia (rectal temperature) had a very similar time-course profile to that of motor incoordination. The time course of hypothermia and motor incoordination was correlated with neither free [3H]DFP nor bound [3H]DIP concentrations in the brain, nor with cholinesterase inhibition in brain. These findings suggest that non-cholinesterase bound [3H]DIP may contribute to the depression of these centrally mediated effects.
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PMID:Relationship between the pharmacological effects and the biodisposition of [3H]diisopropylfluorophosphate in mice after inhalation. 403 91


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