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

Seventeen myasthenia gravis and seven control patients were studied mechano (MMG)- and electromyographically (EMG) during isoflurane/oxygen/air anaesthesia. In myasthenic patients the mean train-of-four ratio and neuromuscular block (by MMG) during 1.9 MAC isoflurane anaesthesia were 55 +/- 9% and 46 +/- 12%, respectively. The correlation between simultaneous MMG and EMG measurements was excellent (r2 = 0.933, P less than 0.001). The occurrence of HLA-B8 together with acetylcholine receptor antibodies seems to predispose myasthenic patients to a neuromuscular depression produced by isoflurane. Our current and prior results show that isoflurane possesses approximately twice as strong a neuromuscular blocking effect as halothane in myasthenic patients.
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PMID:Neuromuscular effects of isoflurane in patients with myasthenia gravis. 230 13

The actions of phencyclidine [1-(1-phenylcyclohexyl)piperidine, PCP] and its morpholine analog [1-(1-phenylcyclohexyl)morpholine, PCM] on ionic currents of nicotinic acetylcholine receptors were studied at the neuromuscular junction of frog skeletal muscle and on embryonic rat muscle cells in tissue culture. PCP and PCM reduced the peak amplitude and the decay time constant of the endplate current (EPC). PCP produced a voltage-dependent curvature and a time-dependent hysteresis loop at negative potentials (at potentials from -50 to -150 mV). In contrast, PCM caused a depression of EPC peak amplitude, but the current-voltage relationship (+60 to -150 mV) remained linear. When PCP-modified EPCs were elicited in trains at hyperpolarized potentials the amplitudes of successive events were progressively decreased and the magnitude of the decrease was dependent on the level of hyperpolarization. At positive potentials the process was reversed; the amplitude increased with successive stimulations. The EPC decayed exponentially in the presence of PCP and PCM, with a shortened time constant of decay that was less dependent on membrane potential than control. PCP and PCM caused only a 20% decrease of the amplitude of the iontophoretically evoked acetylcholine potential, which was significantly different from that induced by the desensitizing alkaloid perhydrohistrionicotoxin. Both PCP and PCM reduced by 50% the mean channel open time obtained from rat myoballs, giving a potency ratio for PCP to PCM of 2.5. This relative potency was correlated with that obtained for the reduction in the decay time constant of the EPC (ratio = 2.2). The effects of PCP on the peak amplitude of the EPC seem to be related to a conformational change of the acetylcholine receptor occurring before channel activation and not to a receptor desensitization.
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PMID:Voltage- and time-dependent effects of phencyclidines on the endplate current arise from open and closed channel blockade. 242 53

Interactions of the oximes pyridine-2-aldoxime (2-PAM) and 1-(2-hydroxyiminomethyl-1-pyridino)-3-(4-carbamoyl-1-pyridino++ +)-2-oxapropane dichloride (HI-6), reactivators of phosphorylated acetylcholinesterase enzyme, with the nicotinic acetylcholine receptor-ion channel complex were studied using electrophysiological techniques. Single channel studies revealed that both oximes increased the opening probability of channels that were activated by acetylcholine. The oximes reduced mean channel open time and burst time in a concentration- and voltage-dependent manner. End-plate current amplitude was increased by 2-PAM (10-100 microM) and HI-6 (1 microM) but depressed at higher concentrations of these agents. The oximes decreased the time constant of end-plate current decay, particularly at hyperpolarized membrane potentials. HI-6 depressed indirect twitch response of the sartorius muscle, whereas 2-PAM caused a facilitation followed by depression. Both agents directly hydrolyzed acetylthiocholine, in addition to weakly inhibiting acetylcholinesterase. Our study demonstrates a direct molecular interaction of the oximes HI-6 and 2-PAM with the natural agonist molecule and with the acetylcholine receptor-ion channel complex. These effects can explain the excitatory and inhibitory actions of both agents, and may form the basis for their antidotal effectiveness against organophosphorus poisoning. The quantitative differences between the effects of 2-PAM and HI-6 on the above parameters are important in view of their differential antidotal efficacies.
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PMID:Acetylcholinesterase reactivators modify the functional properties of the nicotinic acetylcholine receptor ion channel. 245 74

The effects of applications of carbachol on evoked synaptic responses recorded in the dentate gyrus of guinea pig hippocampal slices were examined. Carbachol depressed potentials recorded extracellularly in the medial perforant path terminal zone, but did not significantly alter field potentials recorded in the lateral perforant path terminal zone. Carbachol-induced depression was reversed by applications of the muscarinic antagonists, atropine or pirenzepine. It was suggested that the difference observed in carbachol-induced depression of medial versus lateral perforant path field potentials may be due to regional differences in acetylcholine receptor distribution in the molecular layer of the dentate gyrus.
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PMID:Carbachol depresses synaptic responses in the medial but not the lateral perforant path. 270 73

The effects of nicotine antagonists on single twitches, trains of four twitches and tetanic contractions of the isolated diaphragm of the rat were examined. Different drugs were found to produce different amounts of tetanic fade relative to depression of twitch tension. The order of activity from most able, to least able to produce fade was: hexamethonium greater than trimetaphan=atracurium=tubocurarine greater than pancuronium greater than erabutoxin b. The effect of erabutoxin b was distinctive for its almost complete lack of tetanic fade. 3,4-Diaminopyridine increased tetanic fade produced by tubocurarine, atracurium and hexamethonium, but not that produced by erabutoxin b. It is concluded that nicotinic antagonists act at more than one site at the neuromuscular junction. Assuming block of the postjunctional acetylcholine receptor produces tension depression, a second or third site must be involved in producing tetanic fade. The possibility that tetanic fade results from block of the ion channel associated with the postjunctional acetylcholine receptor or from the block of a prejunctional nicotinic receptor is discussed.
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PMID:Nicotinic antagonists produce differing amounts of tetanic fade in the isolated diaphragm of the rat. 287 97

During endolaryngeal microsurgery, an attempt was made to quantify laryngeal muscle relaxation by electromyographic recording of evoked responses from the vocal cord musculature in 5 patients. Both mechanographic and electromyographic recordings from the adductor pollicis were obtained simultaneously. Following a bolus dose of vecuronium (60 micrograms/kg, n = 3, and 100 micrograms/kg, n = 2), nearly total (97%-100%) suppression of evoked responses at the peripheral muscle site was observed; the vocal cords, however, did not show complete neuromuscular (nm) blockade, but rather varying degrees of nm depression ranging from 61%-92%. The present results clearly show that quantitative information as to duration and degree of neuromuscular depression in the vocal musculature may be obtained by electromyographic recordings of evoked potentials in the clinical setting; it is impossible however, to quantitatively estimate the extent of intrinsic laryngeal muscle relaxation from peripheral nm depression. The pharmacodynamic differences observed might be due to the varying acetylcholine receptor density of the muscle groups studied.
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PMID:[The pharmacodynamics of vecuronium on the musculature of the vocal cords and the ball of the thumb. Preliminary report]. 288 May 25

The effects of phencyclidine(PCP) on the post-tetanic potentiation(PTP) of twitch tension were studied on the isolated mouse phrenic nerve diaphragm preparation. Phencyclidine increased directly elicited twitch tension while it decreased post-tetanic potentiation of the indirectly elicited twitch tension. The maximal depression effect of the PTP was found after higher frequencies and longer durations of stimulation. After repetitive stimulation, the amplitude of endplate potential was potentiated. Phencyclidine decreased the post-tetanic potentiation of the amplitude of endplate potential while the quantal content of the endplate potential was not affected. 4-Aminopyridine increased both directly and indirectly elicited twitch tension while it did not inhibit the post-tetanic potentiation of the twitch tension. It is concluded that phencyclidine suppressed the post-tetanic potentiation of the indirectly elicited twitch tension. The depressant effect may be mainly due to its effect on the acetylcholine receptor-ionic channel complex of the motor endplate.
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PMID:Effect of phencyclidine on post-tetanic twitch tension of the mouse diaphragm preparation. 303 6

We studied the effect of 4-phorbol 12-myristate 13-acetate (PMA) on endothelium-dependent relaxation of rabbit isolated lobar pulmonary arteries contracted with phenylephrine. After full development of relaxation in response to 1.0 microM acetylcholine, addition of 10.0 nM PMA reversed relaxation rapidly and completely. This effect of PMA on acetylcholine-induced relaxation was unchanged when catalase was included in the medium. In separate groups of experiments, lobar pulmonary arteries were preincubated with 10.0 nM PMA for 20 min and then challenged with acetylcholine without washout of PMA. In these experiments PMA did not block completely the relaxation in response to addition of 1.0 microM acetylcholine. Log-concentration response curves for 0.01 to 31.6 microM acetylcholine vs. relaxation as percentage of phenylephrine-induced tone exhibited rightward shifts and depression of maxima after pretreatment with PMA. The EC50 for acetylcholine-induced relaxation was increased from 57 +/- 9.0 to 377 +/- 6.30 nM (values are mean +/- S.E.). Relaxation of lobar pulmonary arteries induced by 10.0 nM A23187 was much less sensitive to treatment with PMA than relaxation induced by acetylcholine. At least for the low concentration of PMA used here, these data are consistent with the following: 1) PMA blocks acetylcholine-induced relaxation by disrupting the link between acetylcholine receptor occupancy and the formation or release of the endothelium-derived relaxing factor, 2) PMA does not directly block the relaxant action of endothelium-derived relaxing factor on vascular smooth muscle and 3) the effect of PMA on acetylcholine-induced relaxation is not mediated by hydrogen peroxide or derived oxygen radicals.
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PMID:Antagonism of acetylcholine-mediated relaxation of rabbit pulmonary arteries by phorbol myristate acetate. 314 10

The effects of so-called postsynaptic snake alpha-neurotoxins (alpha-bungarotoxin, cobratoxin, erabutoxin b) on the wanings of tetanic contraction (tetanic fade) and the run-down of end-plate potentials during stimulation at 100 Hz were studied, respectively, in intact and cut mouse phrenic nerve-diaphragm preparations. No tetanic fade was evident with high concentrations of toxins until the complete failure of contractile response whereas the tetanic fade was evident after prolonged incubation with lower concentrations of toxins. The proportion of junctions exhibiting end-plate potential run-down increased progressively during toxin incubation. However, depression of end-plate potential amplitude by the toxins was not necessarily accompanied by run-down. The tetanic fade and the run-down became more pronounced for a time shortly after washout of toxins despite the restoration of single twitches and end-plate potential amplitudes, indicating the presynaptic origin of these effects induced by alpha-neurotoxins. We demonstrated that the functions of the pre- and postsynaptic acetylcholine receptors can be dissociated by using the different kinetics of toxin-receptor interactions. The results also implicate that a positive feedback enhancement of transmitter release operates via the presynaptic acetylcholine receptor in the neuromuscular junction in normal physiological conditions during repetitive pulses.
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PMID:Dissociation of the end-plate potential run-down and the tetanic fade from the postsynaptic inhibition of acetylcholine receptor by alpha-neurotoxins. 367 29

A term infant required intubation for respiratory depression. Examination revealed hypotonia and areflexia with intact extraocular movements. Electrodiagnostic studies demonstrated defective neuromuscular transmission characterized by borderline low motor evoked amplitudes, profound decremental responses at all stimulation rates, and moderate facilitation (50 to 740%) 15 seconds after 5 seconds of 50 Hz stimulation. Repetitive muscle action potential responses were not recorded following stimulation of nerves by single shocks. Sensory evoked responses and needle electromyographic findings were normal, as were acetylcholine receptor antibody levels. Results of muscle histochemical analyses, including acetylcholinesterase stains, were normal. End-plate histometric analyses demonstrated only a slight reduction in mean synaptic vesicle diameter compared with that in an adult control subject. In vitro muscle contractile properties, stimulating the muscle directly, were normal. Anticholinesterase medications were ineffective. Guanidine produced clinical deterioration. The amplitude of motor evoked responses progressively declined, whereas the percentage of decrement and amount of post-tetanic facilitation increased. Although the nature of the transmission defect was not identified, the data are consistent with abnormal acetylcholine resynthesis, mobilization, or storage without abnormality of release or receptors.
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PMID:Abnormal neuromuscular transmission in an infantile myasthenic syndrome. 608 19


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