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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics and anticholinesterase properties of a single oral dose 6 mg/Kg of technical phenamiphos [ethyl 4-(methylthio)-m-tolyl isopropylphosphoramidate] were investigated in male rats. Animals were killed at each time intervals of 0.5, 1.0, 1.5, 3, 6, 12, 24, 48, and 72 hrs after dosing. The total recovered amount of phenamiphos from brain and plasma tissues reached high level at the first time interval and disappeared biexponentially from both tissues to low level at the end of the experiment. Brain tissue has a greater affinity to phenamiphos than plasma tissue. The half-life of the elimination of phenamiphos from brain and plasma were 100 and 212 hr corresponding to the rate constant values of 0.01 and 0.003 hr-1, respectively. Plasma AUC (area under the curve) value was 1239.81 micrograms hr/L, explaining there was no tendency for the compound to accumulate in the brain tissue (AUC = 774.38 micrograms hr/Kg) compared to the plasma. On the other hand, determination of cholinesterase activity showed that, phenamiphos inhibited the enzymes in both brain and plasma, where the depression of ChE activity was usually more marked in plasma than in brain.
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PMID:Pharmacokinetic profile and anticholinesterase properties of phenamiphos in male rats. 161 16

Twenty anephric and 20 healthy patients received a bolus dose of mivacurium 150 micrograms kg-1. When the first EMG response (T1) of the train-of-four had recovered to 5% of control (T0), an infusion of mivacurium 10 micrograms kg-1 min-1 was started and adjusted to keep T1 at 5%. Ten patients in each group were given neostigmine 35 micrograms kg-1 when the infusion was stopped when T1/T0 had recovered to 20%; in the others recovery was spontaneous. After the bolus dose of mivacurium, mean (SD) depression of T1 was greater in the anephric group than in the normal group (98.4 (3.5) vs 96.8 (4.4)%; P less than 0.01) and recovery of T1/T0 to 5% was slower (15.3 (6.9) vs 9.8 (3.5) min; P less than 0.01). Anephric patients required a slower infusion rate (6.3 (1.9) vs 10.4 (2.8) micrograms kg-1 min-1; P less than 0.001). Neostigmine hastened recovery of both T1/T0 and T4/T1 in both groups. Spontaneous recovery of T1/T0 (from 25% to 75%) after the infusion was also slower in anephric patients (12.2 (8.2) vs 7.7 (1.2) min; P less than 0.05). Plasma cholinesterase activity was less in the anephric group (785 (207) vs 943 (217) iu litre-1; P less than 0.05) and there was a (negative) correlation overall between cholinesterase activity and time to 5% recovery of T1/T0 after the bolus dose (r = -0.42; P less than 0.02). We conclude that patients with chronic renal failure may require a reduced dose of mivacurium.
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PMID:Use of mivacurium chloride by constant infusion in the anephric patient. 164 38

The effects of soman, sarin and VX were examined on ganglionic transmission through paravertebral chain ganglia of the bullfrog, Rana catesbeiana. Low frequency (0.1 Hz), short (2 sec) and long (10 sec) trains of preganglionic stimulation, after exposure to the agents, induced repetitive activity in the extracellularly recorded compound action potential. An irreversible transient depression was observed after exposure to the agents during the first second of short and long stimulus trains. Long stimulus trains of high frequency were required to produce a rundown in the amplitude of the compound action potential, whether recorded in the presence of each agent (10 microM) or following a wash with agent-free solution. The rundown of the compound action potential was use-dependent and not blocked or reversed by atropine (10 microM). Intracellular recordings, in the presence of either soman or VX, demonstrated (1) an increase in the amplitude of the residual excitatory postsynaptic potential or current evoked by synaptic stimulation, (2) an increase in the amplitude and duration of the acetylcholine-induced potential, (3) no increase in either the amplitude or duration of the carbachol-induced potential, (4) repetitive firing with orthodromic but not antidromic stimulation and (5) a concentration- and frequency-dependent depolarization of individual ganglion neurons with orthodromic stimulation which resulted in a decrease in the generation of action potentials. These results suggest that the agent-induced decrease in the compound action potential occurred as a consequence of activity-dependent depolarization of ganglion neurons, which occurs after inhibition of cholinesterase.
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PMID:The effects of irreversible acetylcholinesterase inhibitors on transmission through sympathetic ganglia of the bullfrog. 166 71

1. Acetylcholine (ACh), 7.5 x 10(-5) M, and carbachol, 5 x 10(-6) M (CCh) depressed the frequency of miniature endplate potentials (m.e.p.ps) in the frog (Rana temporaria) sartorius neuromuscular junction with active acetylcholinesterase to about 50-55% of the controls. 2. A similar depression was produced by the nicotinic agonists, nicotine, suberyldicholine and tetramethylammonium. 3. The muscarinic agonists, oxotremorine, methylfurmethide and methacholine were without effect on m.e.p.p. frequency. The muscarinic antagonist, atropine and the nicotinic antagonist, (+)-tubocurarine, had no effect on the depression of m.e.p.p. frequency evoked by CCh. 4. The ganglionic blockers, benzhexonium and IEM-1119, were also without effect on the CCh-evoked depression of m.e.p.p. frequency. 5. Pretreatment of muscles with anticholinesterases did not prevent the CCh-induced drop in m.e.p.p. frequency. 6. The effect of CCh was proportionally the same as in the controls in preparations where the m.e.p.p. frequency was changed by elevation of K+ and in the presence of theophylline, noradrenaline, dibutyryl adenosine 3':5'-cyclic monophosphate (db cyclic AMP) and db cyclic GMP. 7. An inhibitor of Na+,K(+)-ATPase, ouabain, 5 x 10(-5) mol l-1, prevented or reversed the depression of m.e.p.p. frequency by CCh. However, the depression was present in a nominally K(+)-free medium. Insulin and adrenaline, which are considered to be Na+,K(+)-ATPase activators, were without effect on depression of m.e.p.p. frequency. 8. The depression of m.e.p.p. frequency by 5 x 10(-6) M CCh was the same at temperatures between 5 and 30 degrees C with a Q10 near to 1.0. When threshold amounts of CCh were used (6 x 10-7 and 3 x 10-7 M), the depression was less at higher temperatures.9. The receptive structures responsible for the CCh (or ACh)-evoked depression of m.e.p.p. frequency differ pharmacologically from muscarinic, nicotinic ganglionic and neuromuscular junction ACh-receptors as well as from the synaptic cholinesterase, in contrast to previous reports (Duncan & Publicover, 1979).The low temperature-dependence points to the possibility that physical rather than biochemical processes are limiting in this presynaptic effect of cholinomimetics.
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PMID:Depression of miniature endplate potential frequency by acetylcholine and its analogues in frog. 166 83

This study examined the relationship between inhibition of cholinesterase activity (CA) and thermoregulatory response in the rat following exposure to the organophosphate (OP), diisopropyl fluorophosphate (DFP). Male Long-Evans rats were injected with DFP dissolved in peanut oil in doses ranging from 0 to 1.5 mg/kg (s.c.). Colonic (Tcol) and tail skin temperature (Ttail) were recorded at 0, 1, 2 and 3 h post-injection. At 3 h post-injection the rat was sacrificed and a blood sample was taken by cardiac puncture and analyzed for CA. There was a biphasic dose effect of DFP on Tcol with slight but significant elevation in Tcol in the dose range of 0.01-0.5 mg/kg and a significant depression in Tcol at doses of 1.0 and 1.5 mg/kg. There was a dose-dependent fall in CA with DFP administration in the erythrocyte, plasma, and whole blood fractions. Hypothermia was associated with 80-87% inhibition in CA, whereas the elevation in Tcol was associated with 20-70% inhibition in CA. DFP also elicited significant elevations in Ttail. Overall, the data fail to demonstrate any clear relationship between inhibition of blood CA and thermoregulatory response following exposure to DFP. However, the elevation in Tcol following relatively low doses of DFP may be of relevance to the frequently reported symptom of fever in humans exposed to OP agents.
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PMID:Relationship between cholinesterase inhibition and thermoregulation following exposure to diisopropyl fluorophosphate in the rat. 175 22

The centrally active cholinesterase inhibitor physostigmine induces a behavioral syndrome which is thought to represent a model of spontaneous depression. In the present acute trial in 6 healthy volunteers, this model depression was accompanied by clearcut cardiovascular, metabolic and neuroendocrine phenomena of stress. The extent of the changes from baseline, however, scarcely correlated between the behavioral and physiologic phenomena. The behavioral and physiological phenomena could not be antagonized by brofaromine, a putative antidepressant reversibly and selectively inhibiting monoamine oxidase A (MAO-A), contrasting to the complete inhibition by the central cholinolytic scopolamine. This is further evidence that antidepressant efficacy depends on long-term adaptive changes secondary to the enhancement of aminergic neurotransmission rather than this enhancement itself.
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PMID:Adrenergic-cholinergic imbalances: the physostigmine-syndrome is not antagonized by the MAO-A inhibitor brofaromine. 196 18

Using the novel smooth muscle-myenteric plexus (smmp) preparation from the guinea-pig colon, it has been possible to measure acetylcholine (ACh) overflow by a radiolabelling technique. The possibility that choline may be a modulator of cholinergic nerve activity in this preparation was investigated by observing its effects on electrically-evoked overflow of [3H]acetylcholine. Choline (72, 144 microM), in concentrations that did not contract the smmp preparation, caused a depression of electrically-evoked [3H]ACh overflow. This effect was unlikely to be due to actions on cholinesterase enzymes by end product inhibition. Choline also produced substantial non-muscarinic elevation of spontaneous [3H]overflow. It is concluded that inhibitory modulation of enteric cholinergic nerve activity by presynaptic muscarinic receptors may not be exclusively mediated by the actions of acetylcholine.
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PMID:Choline is an inhibitory modulator of cholinergic nerve function in guinea-pig colon. 197 24

Acetylcholinesterase inhibitors produce diverse physiologic effects, but lethal exposure consistently produces respiratory failure due to neuromuscular paralysis or depression of respiratory control centers in the medulla. Simultaneous measurement of gastrocnemius muscle contraction and efferent phrenic nerve activity was used to determine the primary cause of respiratory failure produced by neostigmine and diisopropyl fluorophosphate (DFP) in anesthetized cats. Both neostigmine and DFP abolished phrenic nerve activity prior to producing neuromuscular blockade. Furthermore, neostigmine did not alter brain acetylcholinesterase activity and pretreatment with either atropine methylbromide or atropine increased the dose of neostigmine required to abolish phrenic nerve activity. In contrast, DFP abolished brain cholinesterase activity and only atropine inhibited its respiratory effects. Despite the loss of efferent phrenic nerve activity, there is no evidence of a direct effect of neostigmine on respiratory control centers. Neostigmine may instead alter afferent inputs which modulate respiration to produce a reflex respiratory failure.
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PMID:Mechanisms of respiratory failure produced by neostigmine and diisopropyl fluorophosphate. 206 14

Pyridostigmine bromide (Pyr), the current drug of choice in the management of myasthenia gravis, has been suggested for use in Alzheimer's dementia, and as a prophylactic treatment for intoxication with organophosphate cholinesterase inhibitors. The present study was undertaken to evaluate the dose-response and time-course effects of acute oral administration of Pyr over a broad dose range (3-40 mg/kg) on the lever pressing of rats maintained under a multiple fixed-ratio (FR-20) time-out schedule of reinforcement for water reward. The drug produced a dose-dependent biphasic response depression in the overall rate of FR responding. Low doses of Pyr (less than or equal to 12 mg/kg) that caused no gross signs of toxicity only moderately decreased rates of responding, primarily due to a decrease in response rates. Whereas high doses of Pyr (greater than 24 mg/kg) which produced overt signs of peripheral cholinergic intoxication markedly suppressed overall responding, primarily due to cessation of responding. The lowest effective dose of performance disruption was 6 mg/kg, and the ED50 was calculated as 23.3 (17.9-28.7) mg/kg. The time-course data of performance disruption showed that low doses of Pyr (less than or equal to 12 mg/kg) had an onset latency within 40-80 min and a duration of 20-80 min, whereas high doses (greater than or equal to 24 mg/kg) had an onset latency of 20-40 min and a duration greater than 80 min. These results suggest the recommended human therapeutic or prophylactic regimen of 30-120.mg Pyr, orally taken each 8 hours, might adversely affect behavioral performance.
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PMID:Acute effects of oral pyridostigmine bromide on conditioned operant performance in rats. 206 91

Effect of a single i.p. exposure to an organophosphate insecticide, chlorphenvinphos (CVP), in doses of 1.0 and 3.0 mg/kg (one third and one tenth LD50, respectively), on the latency of the paw-lick response (hot plate test) was investigated in rats before and after a short inescapable footshock. The test was repeated twice on the 18th and 19th days after the exposure, i.e. after a time sufficient for a full recovery of cholinesterase activity in the blood and brain. On the first day of testing the groups did not differ with respect to the paw-lick latency before footshock. However, the paw-lick latency after footshock (the index of stress-induced analgesia) was significantly longer in rats exposed to the higher dose of CVP (3.0 mg/kg) than in the control animals. Twenty four hours later, in the control animals, the paw-lick latencies before footshock were shortened in comparison with those recorded on the day before. An opposite effect was observed in the rats exposed to 3.0 mg/kg of CVP. The data suggest that some alterations in the brain functional state may outlast the CVP induced depression of cholinesterase activity.
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PMID:Effects of a single exposure to chlorphenvinphos, an organophosphate insecticide, on hot-plate behaviour in rats. 213 Aug 75


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