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)

1. The amplitudes of end-plate currents (EPCs) in short trains of fifteen to seventeen EPCs at 10 Hz were depressed in the presence of 10 microM-proadifen when acetylcholinesterase (AChE) was inhibited. 2. The proadifen-induced EPC depression was voltage-dependent and the effect was more pronounced at negative membrane potentials. 3. In the presence of proadifen, the mean amplitude of miniature end-plate currents (MEPCs) was reduced by 36% 5 s after the EPC train as compared with MEPCs before the train. 4. Without proadifen, but with inhibited AChE, an increase of temperature from 20 to 26 degrees C and elevation of external Ca2+ from 1.8 to 2.5 mM led to EPC amplitude depression in the train, which was also potential-dependent. 5. After AChE inhibition, proadifen (10 microM) progressively shortened MEPC decay without significant reduction of amplitude up to 40 min of exposition. MEPCs were not affected by proadifen when AChE was active. 6. It is concluded that these postsynaptic effects of proadifen can be explained neither by its action on the resting acetylcholine receptors (AChR) nor on open ion channels but are due to its desensitization-promoting action.
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PMID:Development of desensitization during repetitive end-plate activity and single end-plate currents in frog muscle. 260 Aug 28

Several lines of evidence have implicated acetylcholine (ACh) as one of the neurotransmitters found to be decreased in Alzheimer's disease (AD). Various methods of cholinergic augmentation have been attempted, with mixed results. Tetrahydroaminoacridine (THA), an acetylcholinesterase inhibitor, is currently being investigated at the McGill Centre for Studies in Aging. Preliminary uncontrolled data from a 10-week clinical trial of THA and lecithin, reported elsewhere, suggest a clinically modest but statistically significant beneficial effect on cognition, although problems exist with side effects, particularly gastrointestinal. Since the suggestion by Janowsky in 1972 that cholinergic neurotransmission may exert an inhibitory or depressant effect on mood, the evidence accumulated in the literature has been inconclusive. We undertook to assess several potential pretreatment correlates of depressive symptoms in AD and to monitor the course of these symptoms during the 10 week treatment period, using the Geriatric Depression Scale (GDS) of Brink and Yesavage. Pretreatment GDS scores were found to correlate with degree of overall disability and dementia as measured by the Rapid Disability Rating Scale (RDRS) and the Mini Mental State Examination (MMS), respectively. GDS scores over the treatment period did not change to a statistically significant degree. The meaning of these results is discussed, particularly with reference to the difficulty of diagnosis and measurement of depression in the setting of dementia.
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PMID:Canadian collaborative study of tetrahydroaminoacridine (THA) and lecithin treatment of Alzheimer's disease: effect on mood. 265 61

In high spinal cats, the acute time-dependent changes of both the activity of spinal reflex pathways and the activity of three different esterases (acetylcholinesterase, carboxylesterase and neurotoxicant target enzyme) in the spinal cord were investigated after intravenous application of the organophosphorus compound di-isopropyl phosphofluoridate (DFP). There is no general depression of spinal reflexes by DFP. While the recurrent inhibition is completely abolished for a long time and the reflexes to a flexor (PBSt) are depressed but with a shorter recovery time, the reflexes to an extensor (GS) are distinctly less depressed or even facilitated. Reflex pathways from skin afferents to motoneurones did not react in a uniform way to DFP, e.g. inhibitory nociceptive pathways were less affected than excitatory ones. Esterase activities were heavily depressed and recovered with different time courses. The acute DFP action cannot be explained by a uniform intoxication of all spinal functions but probably emerges from a differential action on different interneuronal systems.
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PMID:Influence of the organophosphorus compound DFP on inhibitory motor systems and esterase activity in the spinal cord of cats. 271 Apr 27

We have studied the action of doxapram on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation. Doxapram augmented neuromuscular transmission in a dose-related manner when a threshold concentration of 5 x 10(-5) mol litre-1 had been exceeded. The activity of the acetylcholinesterase in rat diaphragm has been examined also in the presence of doxapram. No inhibitory effect was seen in the concentration range which augmented neuromuscular transmission, thus excluding cholinesterase inhibition as the underlying mechanism. In contrast, in the presence of partial neuromuscular block, a dose-related depression of neuromuscular transmission with doxapram was revealed. This was greatest when the neuromuscular blocking agents possessed significant presynaptic activity (beta-bungarotoxin and tubocurarine). In this situation any facilitatory action of doxapram was severely reduced or abolished. In contrast, the facilitatory effects of doxapram were apparent in the presence of partial block produced by agents with less or no presynaptic activity (pancuronium and alpha-bungarotoxin). This study suggests that doxapram has a presynaptic facilitatory action at the neuromuscular junction. In the presence of partial neuromuscular block, an inhibitory action is revealed which may be post-junctional. The concentrations of doxapram at which these effects appear are approximately five times greater than those reached in plasma after a standard clinical dose.
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PMID:Doxapram and the neuromuscular junction. 231 31

Postsynaptic effects of vinblastine (VB) and colchicine (CCH) were studied in the frog neuromuscular junction under voltage-clamp conditions. The same concentrations of VB and CCM, which did not affect the amplitude and duration of miniature end plate currents (MEPC), the current-voltage relationship of peak end plate currents (EPC) and voltage sensitivity of the decay phase of EPC, markedly reduced the responses to iontophoretic application of acetylcholine. Both VB and CCH accelerated the EPC decay when acetylcholinesterase was inhibited; they also caused a pronounced depression in the trains of EPC (10 Hz) and trains of responses to acetylcholine application (5-10 Hz). It was concluded that use-dependent effects of VB and CCH are not connected with their influence on the cytoskeleton of the muscle fibre, but can be a result of accelerated desensitization of cholinoreceptors.
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PMID:[Effect of vinblastine and colchicine on the postsynaptic membrane of the myoneural junction in the frog]. 283 69

The organophosphorus compounds diisopropylphosphorofluoridate (DFP) and isopropylmethylphosphonofluoridate (sarin) depressed the monosynaptic reflex (MSR) in spinal cords from 7- to 9-day-old male rats. The concentrations of DFP and sarin which depressed the MSR by nearly 50% were 100 microM and 100 nM, respectively. Simultaneous superfusion of the cords with thyrotropin-releasing hormone (TRH) with either DFP or sarin resulted in a reversal of the depression. The depression caused by DFP was reversed to 95% of control by 100 nM TRH whereas similar reversal of sarin-induced depression required a 10-fold greater concentration of TRH. The potentiating effect of TRH was not affected by atropine even at a high concentration (1 microM) although atropine easily reversed organophosphorus-induced depression of the MSR. It appears that reversal of organophosphorus-induced depression by TRH might occur through a noncholinergic, TRH-sensitive receptor mechanism and may be unrelated to acetylcholinesterase activity. This action represents a possible utility of TRH as an adjunct in organophosphorus toxicity.
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PMID:Segmental synaptic depression caused by diisopropylphosphorofluoridate and sarin is reversed by thyrotropin-releasing hormone in the neonatal rat spinal cord. 284 64

Organophosphorus inhibitor of acetylcholinesterase (AChE) armin (1 x 10(-6) M) induced a variety of pre- and postsynaptic effects resulting from the AChE inhibition and subsequent accumulation of acetylcholine (ACh) in the synaptic cleft. The intensity of postsynaptic effects (level of neuron depolarization, degree of action potential depression) was shown to be different in the ganglia of frog and rabbit. This could be explained by differences in the total amount of ACh released in response to nerve stimulation as well as at rest. Both muscarinic and nicotinic cholinoreceptors were involved in the process of sustained depolarization of the neurons in the rabbit superior cervical ganglion after AChE inhibition. In frog ganglion neurons the nicotinic receptors did not participate in depolarization evidently due to their fast desensitization. The activation of presynaptic muscarinic receptors resulted in decrease of ACh released by nerve stimulation seems to weaken depolarization and blockade of synaptic transmission in sympathetic ganglia treated by AChE inhibitors.
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PMID:[Comparative research on synaptic transmission in the sympathetic ganglia of rabbits and frogs during acetylcholinesterase inhibition]. 285 Dec 43

The effect of physostigmine on the loss of consciousness and respiratory depression induced in rabbits by flunitrazepam, 1 mg/kg, was studied to demonstrate whether the restoration of consciousness and respiration rate results from an increase in central cholinergic activity or from an interference by physostigmine with specific binding of flunitrazepam to its receptors. Physostigmine, 0.1-0.4 mg/kg iv, caused a dose-related reversal of consciousness and respiration rate within 15 min of its injection, which lasted 15-30 min depending on the dose. This was associated with peak inhibition of acetylcholinesterase (AChE) in the frontal cortex and medulla, at 15 min, ranging from 35-51%. The analeptic effect of physostigmine in flunitrazepam-treated rabbits was prevented by pretreatment with scopolamine, 1 mg/kg. The effective dose range for physostigmine, 3-12 mumol/kg, is close to concentrations of this agent that inhibit activity in solubilized preparations of AChE from rabbit cortex, 1-3 X 10(-8) M. However, physostigmine, 10(-9) -10(-4) M, failed to displace 3H flunitrazepam from specific binding sites on membranes prepared from rabbit cerebral cortex. It is concluded that physostigmine antagonizes the somnolence and respiratory depression induced by benzodiazepines by restoring cholinergic transmission to normal levels. The effective dose range of physostigmine is small, and serious side effects from overdose can occur as a result of excess cholinergic activity at neuromuscular synapses.
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PMID:Mechanism of antagonism by physostigmine of acute flunitrazepam intoxication. 300 60

The effects of acute doses of soman (40, 60, or 80 micrograms/kg sc) in rats were evaluated for toxic symptoms as well as for changes in plasma levels of glucose, insulin, glucagon, corticosterone, norepinephrine, and epinephrine. The relationship between changes in these levels and depressed acetylcholinesterase activity in the hypothalamus was determined. Soman 40 micrograms/kg did not manifest significant changes in any of the parameters evaluated. However, both the 60 and 80 micrograms/kg doses of soman caused dose- and time-related increases in plasma levels of glucose, corticosterone, norepinephrine, epinephrine, and a depression of insulin. Many of these increases, as well as the severity of toxicity, appear to be inversely related to the hypothalamic acetylcholinesterase levels. The hyperglycemia following the higher doses of soman is likely due to the combined effects of elevated levels of corticosterone, catecholamines, possibly glucagon, and depressed insulin levels. Stress from the toxic effects of soman is likely partially responsible for the endocrine effects since most of the changes observed are consistent with changes in these levels that would be manifested in an animal stress model.
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PMID:Effect of acute soman on selected endocrine parameters and blood glucose in rats. 306 86

Our purpose was to examine the influence of inhibition of cholinesterase at the ventral surface of the medulla on cardiorespiratory activity in the chloralose-anesthetized cat. Administration of the anticholinesterase agent, diisopropylfluorophosphate (DFP) to areas responding to acetylcholine (i.e., rostral and caudal chemosensitive areas of the ventral surface of the medulla) in doses ranging from 12.5 to 50 micrograms bilaterally had minimal effects on cardiorespiratory activity. However, similar doses applied to the intermediate area of the ventral surface of the medulla produced an increase in tidal volume and hypotension. For example, a dose of 12.5 micrograms increased tidal volume by 14 +/- 3 ml (P greater than .05). Similar responses were seen with higher doses of DFP; in addition, respiratory depression (apnea) also occurred. This depression was characterized by a slowing in respiratory rate. The organophosphate compound, soman, in doses of 0.25 and 0.5 micrograms produced effects similar to those seen with DFP with the exception that an increase in respiratory rate was observed before the decrease in respiratory rate occurred. In addition, a greater degree of hypotension was observed with soman as compared to DFP. Findings comparable to those obtained with DFP were produced by the muscarinic receptor agonist, oxotremorine (0.077-10 micrograms). The effects of DFP, soman and oxotremorine were counteracted by locally applied atropine. In addition, measurements of acetylcholinesterase activity taken from the rostral, intermediate and caudal areas indicate a relatively low activity at the rostral area but a relatively high activity at the intermediate area.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiorespiratory effects produced by activation of cholinergic muscarinic receptors on the ventral surface of the medulla. 318 70


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