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)

Acute intraperitoneal administration of lanthanum chloride to newborn chicks at the single dose of 250 mg/kg body weight inhibits calcium binding to brain synaptosomal membrane. There is also marked depression in the activities of neural Ca2+-ATPase, Mg2+-ATPase, and cholinesterase after acute lanthanum chloride intoxication. The inhibition of these enzymes in relation to depletion of calcium binding to the synaptosomal membrane has been discussed.
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PMID:Neurotoxicity of lanthanum chloride in newborn chicks. 613 Jun 44

Atracurium, a new non-depolarizing neuromuscular blocking agent, was studied in 70 patients anesthetized with fentanyl, thiopental, and nitrous oxide-oxygen. The dose found to produce 95% twitch inhibition (ED95) was 0.2 mg/kg. The onset time from injection to maximum depression of twitch was 4.0 minutes at this dose; the duration to 95% recovery was 44.1 minutes. Twice the ED95 dose (0.4 mg/kg) had an onset time of 1.7 minutes and a duration of 63.5 minutes. No cardiovascular effects were observed in this dosage range. At higher doses (0.5 and 0.6 mg/kg) arterial pressure decreased 13% and 20% and heart rate increased 5% and 8%, respectively. Sixteen patients received at least four successive doses of atracurium. No clinically significant cumulative effect could be shown when recovery from 25% to 75% of control twitch height was compared for initial and final doses in the series. Atracurium spontaneously decomposes at physiologic pH via the Hofmann elimination reaction and may also undergo ester hydrolysis independent of plasma cholinesterase. These proposed pathways of inactivation may explain the lack of cumulative effect and the drug's intermediate duration of action. Based on the results of this study, atracurium offers several clinical advantages and should undergo more extensive clinical trials.
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PMID:Clinical pharmacology of atracurium besylate (BW 33A): a new non-depolarizing muscle relaxant. 621 81

The possibility that acetylcholine (ACh) may inhibit its own release from nerve terminals by acting on presynaptic receptors has been investigated using the electric organ of Torpedo marmorata. ACh release was analysed by electrophysiological and biochemical methods conjointly. Oxotremorine, at micromolar concentrations, depressed nerve-electroplaque transmission by reducing the amount of ACh released by nerve impulses. This effect was competitively antagonised by nanomolar concentrations of atropine or methylatropine. Other muscarinic agonists, betanechol, pilocarpine and muscarine, however, failed to depress transmission but choline was effective at high concentrations. Anticholinesterase drugs, physostigmine, neostigmine or fluostigmine (diisopropylfluorophosphate, given as pretreatment and subsequently washed out) markedly depressed evoked ACh release. When cholinesterase was inhibited, the addition of oxotremorine or exogenous ACh caused a further depression of ACh release. Atropine was found to be very effective in reversing the depression of transmitter release produced by anticholinesterases. Looking for the mechanism of these presynaptic changes, we found that oxotremorine had little, if any, effect on the size of the ACh store of the tissue, on the compartmentation of ACh inside and outside synaptic vesicles, or on the rate of ACh turnover. The changes induced by oxotremorine cannot be explained by a reduction in calcium entry, since the presence of oxotremorine did not change the uptake of 45Ca observed after repetitive stimulation. Electrophysiological techniques were used to test for an effect of atropine in experiments where transmission of one impulse was expected to depress ACh release by subsequent impulses. This depression was not affected atropine, making it unlikely that the 'muscarinic' inhibition of ACh release has a role as a short-term feedback regulation of transmission. A second possibility is that oxotremorine (and external non-hydrolysed ACh) can enter the presynaptic membrane and interfere with the mechanism of transmitter release.
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PMID:Cholinergic inhibition of acetylcholine release in the electric organ of Torpedo. 628 Oct 33

1. Age changes in spontaneous and evoked transmitter release, in receptor number and in ultrastructure at the neuromuscular junction were studied in the CBF-1 mouse strain, which stays physically active and relatively free of organ pathology into advanced age.2. Spontaneous miniature end-plate potentials (m.e.p.p.s) were recorded in the following young (8-12 months) and old (29-33 months) mouse muscles: extensor digitorum longus (e.d.l.), soleus (sol.), gluteus maximus (g.m.), diaphragm (diaph.) and extensor digitorum communis (e.d.c.).3. M.e.p.p. amplitudes were unchanged with age in four muscle groups despite increases in input resistance (in e.d.l., sol. and g.m.). M.e.p.p. amplitude in old diaph. increased 54% with no change in input resistance. Bimodal distributions of m.e.p.p. amplitudes were observed in 6-23% of muscle fibres but were not more prevalent in old mice. There was little or no change in resting membrane potential with age.4. Numbers of junctional acetylcholine receptors (measured with (125)I-alpha-bungarotoxin) were the same in all young and old muscles except e.d.l., where a 30% decrease was noted. Extrajunctional receptors and other indicators of denervation (decreases in resting potential, twitch tension or muscle fibre diameter) were absent or minimal.5. M.e.p.p. frequency decreased in e.d.l., sol. and e.d.c. but not in g.m. or diaph. There was no correlated change in the cholinesterase-positive end-plate area.6. It is concluded that m.e.p.p. amplitude is maintained in old muscles by a combination of compensatory changes. The decline in m.e.p.p. frequency varies between muscle groups and is independent of the length of the motoneurone axon or level of innervation.7. Evoked end-plate potentials (e.p.p.s) were recorded in e.d.l., sol. and diaph. from young (11-13 months) and old (29-30 or 34-35 months) male CBF-1 mice in curarized preparations stimulated at 2 or 20 Hz. The amplitude of the initial e.p.p. of the trains was increased by 122% in old e.d.l. and 93% in old sol., and plateau e.p.p. amplitudes were also increased by about 100% (e.d.l.) and 67% (sol.). This, combined with the absence of change in m.e.p.p. amplitude with age, suggests that the number of quanta released per nerve impulse was increased. In diaph. there was no change with age.8. In all muscle groups, the threshold for initiation of the muscle action potential was unchanged with age. Thus, the relative safety factor of transmission was increased in curarized old e.d.l. and sol. (but not diaph.).9. Depression of the indirect twitch in solutions with a decreased calcium: magnesium ratio was also used as a relative measure of synaptic efficacy. Old sol. and e.d.l. but not diaph. muscles showed less depression of indirect twitch amplitude than did young muscle under these conditions.10. In cut-fibre preparations of sol. and diaph. stimulated at 20 Hz, there was no age-dependent difference in e.p.p. amplitude, in directly measured quantal content, or in curare sensitivity. In view of other results, these findings require careful interpretation.11. Ultrastructural morphometry was carried out in e.d.l. The nerve terminals in old (30 and 34 months) e.d.l. muscles exhibited pronounced loss of synaptic vesicles. In 34-month animals, decreased nerve terminal area and post-synaptic folds devoid of nerve terminals were often observed. Since no evidence of denervation was found by physiological criteria, it is concluded that in 34-month mice, nerve terminals withdraw from some synaptic gutters but do not abandon any junction entirely. The large presynaptic ultrastructural changes contrast with the physiological data showing no deficit and even increases in transmitter release. Therefore, under these conditions, these profound structural changes are either not functionally significant or are well compensated.
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PMID:Neuromuscular transmission and correlative morphology in young and old mice. 631 88

Presynaptic effect of compound application of the cholinesterase (ChE) inhibitors of the reversible (galanthamine) and the irreversible (armin) after galanthamine pretreatment has been studied on the neuromuscular transmission at the rat diaphragm. The experiment conditions were regarded as a model of the preventive action of the reversible ChE inhibitors against organism poisoning by the irreversible ChE inhibitors. The quantal content of the end plate potentials (EPP) decreases under the compound action of inhibitors. But under these conditions the EPP amplitude at the single nerve stimulation increases as compared with the control one. The pronounced presynaptic depression and the block of the neuromuscular transmission are observed at the repetitive stimulation (10-50 s-1). The preventive action of galanthamine against the armin poisoning does not relate to presynaptic processes.
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PMID:[Joint action of reversible and irreversible cholinesterase inhibitors on neuromuscular transmission in the rat diaphragm]. 631 88

Several identified neurons of the Aplysia buccal ganglia respond to choline. Iontophoretic applications of either choline or acetylcholine (ACh) to voltage-clamped inhibitory follower neurons produce similar currents. Peak amplitudes of choline responses were 10-100% of ACh responses on the same cell. Choline currents were curare blockable and reversed at -69 +/- 2 mV, within 1 mV of postsynaptic current (IPSC) reversal. Application of 1 mM choline to the bath produces more prolonged effects than an initial conductance change. Choline depressed IPSC amplitude by 42 +/- 5% and prolonged IPSC decay time constant by 25 +/- 7%. The slowing was reversible but the depression was not. Use of choline as a Na substitute may therefore involve unexpected partial agonist action; even where conductance changes are transient or inapparent, choline may alter synaptic responses. Bath choline had variable effects on cholinergic self-inhibitory synapses, blocking in six trials but not in three others. Voltage clamping cells BL and BR7, in which monosynaptic cholinergic PSPs are diphasic, reveals underlying early inward and late outward currents. Choline activates only the late outward current component. Correspondingly, bath choline blocks only the late outward component, as does eserine and ACh. This block is not seen with neostigmine, and so is unlikely to be related to cholinesterase inhibition. The early inward current component, revealed by block of the late component by choline or ACh, decays exponentially. Decay time constant is exponentially dependent on membrane potential over the range -20 to -100 mV, with 63-mV depolarization speeding decay e-fold. Eserine prolongs decay and steepens voltage dependence. The late outward component decays with voltage-independent time constant of 48 +/- 5 ms. Both the time integral of synaptic conductance and the ratio of synaptic charge transfer to peak synaptic current of the early inward component of the cell 7 response are reduced by depolarization. Voltage-dependent duration thus combines with reduced driving force in diminishing the excitatory effect of this component at depolarized levels, allowing the inhibitory component to predominate. In this diphasic synapse, voltage dependence of the time course of one component thus serves an easily identified function.
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PMID:Choline acts as agonist and blocker for Aplysia cholinergic synapses. 631 20

Phorate (Thimet), an aliphatic derivative of phosphorus is a highly toxic insecticide. In order to implement the safety measures, the clinical manifestations and cholinesterase (ChE) activity were evaluated before and after 2 weeks of exposure to this insecticide in 40 male formulators. The 2 week's exposure reveal signs and symptoms of toxicity in 60% of the formulators. Gastrointestinal symptoms and lowering of heart rate (bradycardia) were more prominent as compared to the neurological symptoms. A significant depression in plasma ChE activity was observed at the end of 1st week (55%) and 2nd week (71%) as compared to the respective pre-exposure values. A recovery up to 79% of the pre-exposure activity of this enzyme was noticed 10 days after cessation of the above exposure.
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PMID:Clinical effects and cholinesterase activity changes in workers exposed to Phorate (Thimet). 647 Apr 23

This study deals with the serum pseudocholinesterase levels of anaesthesiologists and radiologists as compared with those of the general population which has not been exposed to anaesthetic gas traces or radiation. No difference in serum pseudocholinesterase levels was found in any of the three groups studied when compared to each other. In conclusion, anaesthesiologists and radiologists in good physical condition may not present any increased risk of respiratory depression or prolonged apnoea after succinylcholine administration for muscle relaxation, in comparison with the general population which has not been exposed to either anaesthetic gases or radiation.
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PMID:Serum pseudocholinesterase levels in anaesthesiologists and radiologists. 662 Nov 79

Recognition of exposure to imidan was assessed in goats by dialkyl phosphate concentrations, blood cholinesterase (ChE) determinations, and blood imidan concentrations. Groups of three goats received 5.0 mg imidan/kg/day (low dose) or 10 mg imidan/kg/day (high dose) for 7 days orally. One goat received no imidan and one goat received an acute single dose (200 mg/kg). The urine of all treated goats was examined for the excretory dialkyl phosphates, O,O-dimethyl phosphorodithioate (DMDTP) and O,O-dimethyl phosphorothionate (DMTP). The overall mean DMDTP urinary concentration was 19.1 ppm (10-mg/kg treatment group) and 7.2 ppm (5-mg/kg treatment group). These metabolites rapidly disappeared following removal of the treatment except in those goats clinically affected. Milk contained no identifiable concentrations of dialkyl phosphates. Cholinesterase depression was observed in all imidan-treated goats, and a dose effect was observed. No imidan was detected in whole blood of either the 5- or 10-mg/kg treatment groups. Low blood concentrations (ppb) of imidan were measured in the acute single-dose exposed goat. Both urinary DMDTP and blood ChE provided recognition of imidan exposure. DMDTP, however, was immediately present in urine after exposure and provided stronger support for organophosphate exposure than did blood ChE.
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PMID:Comparison of measurement of dialkyl phosphates in milk/urine and blood cholinesterase and insecticide concentrations in goats exposed to the organophosphate insecticide, imidan. 669 74

The acute toxicity of quinuronium was investigated by measurements of lethal doses (LD50) in mice and rats, cholinesterase activity in vivo in whole blood, and protection from anticholinesterase activity by atropinisation in sheep and rabbits. The LD50s in mice injected i.p. and s.c. were 4.80 and 5.40 mg/kg and in rats 6.3 and 6.5 mg/kg for i.p. and s.c. routes, respectively. Signs of salivation, defecation, anorexia and muscular spasms were observed in sheep. In rabbits anorexia and depression only were observed. There was species variation in normal cholinesterase activity, rabbits being low in activity. Quinuronium inhibited cholinesterase activity from 10 min to 24 h after treatment in sheep by 24% of the normal baseline values. The enzyme activity returned to normal at 48 h. Atropinisation partially protected against anticholinesterase activity in sheep; cholinesterase activity was inhibited by only 14% of the normal baseline values 10 min to 2 h after treatment. This study indicates that quinuronium is highly toxic and that rabbits are moderately resistant.
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PMID:Acute toxicity studies with quinuronium sulfate in laboratory animals and sheep. 669 98


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