UMLS:C0011570 - FACTA Search

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

d-Tubocurarine (dTc) was infused intravenously into 35 cats anesthetized with chloralose and urethane at a constant continuous rate to produce and maintain 90 per cent depression of twitch height of the anterior tibial muscle following supramaximal stimulation of the peroneal nerve. The mean infusion rates that produced 90 per cent depression were not significantly altered by respiratory acid-base changes. Metabolic alkalosis decreased (32.5 per cent) and metabolic acidosis increased (27.7 per cent) the required infusion rate of dTc. When pH and Paco2 were maintained at 7.37 and 38 torr, respectively, the addition of a bolus of neostigmine, 10.5 mug/kg, intravenously, to the continuing infusion of dTc produced 50 per cent antagonism of the dTc-depressed twitch. Respiratory alkalosis and metabolic acidosis did not alter the dose of neostigmine needed to produce 50 per cent antagonism. However, during respiratory acidosis (pH 7.13, Paco2 66 torr) and metabolic alkalosis (pH 7.59, Paco2 36 torr) 20.0 and 18.0 mug/kg neostigmine, respectively, were needed to produce 50 per cent antagonism. Still larger doses of neostigmine (75 mug/kg) could not completely antagonize the block unless pH and Paco2 were returned to 7.30-7.50 and 35-45 torr, respectively. It is concluded that respiratory acidosis and metabolic alkalosis limit and oppose antagonism of dTc by neostigmine.
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PMID:The effect of acid-base balance on neostigmine antagonism of d-tubocurarine-induced neuromuscular blockade. 23 27

A new method for monitoring the effect of muscle relaxants on the myoneural junction was tested in unanesthetized volunteers. Evoked electromyographic responses to stimulation, sweeping exponentially from 1 to 100 Hz over 10 seconds, were recorded from the hand and abdominal muscles. d-Tubocurarine (dTc) was given intravenously in incremental doses until head lift was abolished. Thumb twitch tension, vital capacity, peak expiratory flow, maximal inspiratory force, and hand grip strength were recorded during partial paralysis and recovery. The frequency sweep electromyogram (FS-EMG) of the musculus rectus abdominis was more depressed than the FS-EMG of the musculus abductor digiti V at the time head lift was abolished. The abdominal muscle recovered faster from dTc paralysis than did the hand muscle. The latter failed to respond normally to the highest frequencies of stimulation during the entire period of observation lasting 72 minutes after dTc injection. At the time of maximal neuromuscular blockade, respiratory function showed less depression than the FS-EMG of the abdominal muscle.
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PMID:Frequency sweep electromyogram and voluntary effort in volunteers after d-tubocurarine. 83 92

The literature data and personal experience with high - and very high - risk patients show that the association of enflurane as anaesthetic and pancuronium as muscle-relaxant constitutes a positive advance in balanced general anaesthesia. Cardiocirculatory depression is not encountered; if anything, there is an improvement of homeostatic conditions. This results in increased safety, even for patients regarded as inoperable. Confirmation of the reasons for associating these two drugs has certainly been obtained. The method cannot, however, be employed indiscriminately, but, at least in theory, should be avoided in patients with serious hypertension or a myocardium that is particularly sensitive to endogenic catecholamine incretion. In hypotension, on the other hand, cases of imminent or frank shock, or situations where surgery cannot be postponed, the association is, paradoxically, a true pharmacological "support", backed up, of course, by other usual procedures. This contradiction of modern views concerning the peripheral circulation is only apparent, since the duration of anaesthesia is reduced; main aim in this period is the maintenance of sufficient circulation to the more important organs. Comparison with associations combining d-Tubocurarine, halothane and methoxyfluorane is still an open question as far as objective assessment of their usefulness is concerned. There can be no doubt, however, that the association of enflurane and pancuronium has eliminated a large sector of contraindications in the field of general anaesthesia.
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PMID:[Enflurane-pancuronium combination: real progress toward greater safe conditions in general anesthesia]. 111 99

Acetylcholine and nicotine application to the intact pacinian corpuscle failed to stimulate the spike activity, but changed the sensitivity to the mechanical stimulation: low concentration (1.10(-6) g/ml) increased the sensitivity and high concentration (1.10(-4) g/ml) decreased it. This influence can be attributed to the action of these substances on the structures which generate the action potentials. Acetylcholine application to decapsulated pacinian corpuscles stimulated the appearance of the spike activity. This reaction was possibly connected with the acetylcholine influence on the mechanoreceptive zones proper. Tubocurarine or hexonium application of decapsulated pacinian corpuscles led to depression of the sensitivity of the receptor to the mechanical stimulation that can also be explained by the participation of acetylcholine in the process of adequate receptor stimulation.
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PMID:[The effect of cholinergic substances on individual mechanoreceptors--Pacinian corpuscles]. 122 84

The basis for the comparative toxicity to parasitic nematodes and their mammalian hosts of the anthelmintics levamisole, pyrantel, and several related analogs on somatic nicotinic cholinergic transmission was examined. Measurements of muscle contractility and membrane potential were made using the isolated hemidiaphragm preparation of the rat and isolated axial muscle segments from the gastrointestinal nematode Haemonchus contortus. Pyrantel caused a dose- and time-dependent reduction of nerve-evoked twitches in the rat diaphragm. These effects were exacerbated by increasing the frequency of phrenic nerve stimulation from 0.5 to 50 Hz. Levamisole was less potent and the onset of its effects slower than pyrantel. Neither drug significantly affected twitches evoked from d-tubocurarine-blocked preparations following direct stimulation of the diaphragm. Twitch depression was reversed by washing, but not by application of physostigmine. In H. contortus, both drugs stimulated a spastic contraction and sustained paralysis in the concentration range of 1-10 microM, mimicking the action of nicotine. Neither nicotinic nor muscarinic antagonists blocked these responses. Moreover, neither nicotinic antagonists nor muscarinic agonists or antagonists had any independent effect on contractility of the parasite muscle segments. The blocking actions of levamisole and pyrantel on H. contortus axial muscle were associated with membrane depolarization at the muscle. In the rat-isolated hemidiaphragm, pyrantel, but not levamisole, depolarized end-plate regions of muscle fibers. d-Tubocurarine blocked the depolarizing action of pyrantel but not levamisole on rat-isolated hemidiaphragm. In axial muscle fibers of H. contortus, d-tubocurarine did not block the depolarizing actions of pyrantel, levamisole, or nicotine. 3-Bromo and 3-amino derivatives of levamisole were equipotent with and mimicked the actions of the parent compound on H. contortus axial muscle contractility. In the rat preparation, the 3-bromo derivative was more potent than levamisole or 3-amino-levamisole. 3-Amino-levamisole, but not 3-bromo-levamisole, depolarized muscle end-plate membrane in the rat diaphragm. Results of the present study are consistent with the following conclusions: (a) both levamisole and pyrantel block contractility of nematode axial muscle by causing sustained depolarization of the muscle membrane; (b) both drugs block neuromuscular transmission at the mammalian neuromuscular junction but their mechanisms appear to differ; (c) levamisole and pyrantel are more potent blockers of neuromuscular transmission in H. contortus than in the rat. These results suggest that potentially important pharmacological differences exist between nematode and mammalian somatic nicotinic receptors.
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PMID:Comparative neuromuscular blocking actions of levamisole and pyrantel-type anthelmintics on rat and gastrointestinal nematode somatic muscle. 131 Jan 65

1. Whether the function of the postsynaptic acetylcholine receptor is use-dependently affected by repetitive nerve stimulation in the presence of competitive antagonists was studied in the mouse phrenic nerve-hemidiaphragm preparation. 2. For electrophysiological experiments, the preparation was immobilized by synthetic mu-conotoxin, which preferentially blocks muscular Na-channels causing neither depolarization of the membrane potential, inhibition of quantal transmitter release, nor depression of nicotinic receptor function. 3. High concentrations of cobratoxin depressed indirect twitches and endplate potentials (e.p.ps) without inducing waning of contractilities or run-down of trains of e.p.ps evoked at 10-100 Hz. However, waning and run-down were accelerated after washout of the toxin despite diminished postsynaptic receptor blockade. Once the run-down of e.p.ps was produced by washout or low concentrations of cobratoxin, further depression of e.p.p. amplitude with high concentrations of cobratoxin did not attenuate the e.p.p. run-down. 4. The degrees of waning of tetanus and trains of e.p.ps produced by a very high concentration of tubocurarine (20 microM) were also less than that caused at a 100 fold lower concentration, albeit the amplitudes of twitches and the first e.p.p. were depressed more rapidly and markedly. 5. Tubocurarine, like cobratoxin, depressed the amplitude of miniature endplate potentials (m.e.p.ps) more than e.p.ps. 6. In contrast to the steepened run-down of successive e.p.ps in the presence of low concentrations of either nicotinic antagonists, the amplitude of m.e.p.ps observed during repetitive stimulation was uniform and was not different from that before stimulation. 7. The results suggest that the e.p.p. run-down and tetanic fade induced by nicotinic antagonists are due to a slow kinetic blockade of presynaptic receptors and confirm that the e.p.p. run-down is not produced by a use-dependent failure of postsynaptic nicotinic receptors. The roles of the presynaptic nicotinic receptor in positive or negative feedback modulations of transmitter release are discussed.
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PMID:Run-down of neuromuscular transmission during repetitive nerve activity by nicotinic antagonists is not due to desensitization of the postsynaptic receptor. 167 97

1. Nerve-evoked maximal twitches (T1, T2, T3, T4) of the rat isolated hemidiaphragm to train-of-four (TOF) stimulation (2 Hz X 2 s) were recorded continuously in the absence or presence of tubocurarine (1.5 mumol/l), succinylcholine (40 mumol/l) or alpha-bungarotoxin (1 mumol/l). The T1 and T4 response-time profiles for the three drugs were analysed with respect to amplitude depression and the TOF ratio (T4/T1) during the development of and recovery from neuromuscular blockade. 2. Tubocurarine produced T1 block accompanied by intense TOF fade; for the same degree of T1 block, the TOF ratio was lower during the recovery from blockade after washing out tubocurarine from the bath than during the onset of blockade. There was also a correspondingly slower recovery of the TOF ratio from 90% T1 block to control levels when compared with the time for complete T1 recovery. Fade and twitch tension depression were shown clearly to be separate responses, each with its own response-time profile. Fade is therefore not simply a consequence of postjunctional cholinoceptor blockade. 3. Succinylcholine produced T1 block with only moderate TOF fade; similar recovery rates from 90% T1 block to control levels were obtained for T1 and the TOF ratio. 4. alpha-Bungarotoxin produced irreversible and complete neuromuscular blockade during which TOF fade was virtually absent. 5. The results obtained in this study closely resemble those from other similar studies in animals and in humans and clearly demonstrate that the rat isolated hemidiaphragm is a suitable in vitro model for time course studies on TOF fade.
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PMID:Train-of-four fade during neuromuscular blockade induced by tubocurarine, succinylcholine or alpha-bungarotoxin in the rat isolated hemidiaphragm. 285 17

Effects of isepamicin sulfate (HAPA-B), a new aminoglycoside antibiotic, on the neuromuscular transmission were studied in rats and compared with those of amikacin (AMK) or other aminoglycoside antibiotics. The HAPA-B, as well as other aminoglycoside antibiotics, depressed the twitch response of diaphragm to phrenic nerve stimulation in vitro. The depression effects of different drugs were compared and graded in the order of strengths of blocking action as: netilmicin (NTL) greater than gentamicin (GM) greater than streptomycin (SM) greater than kanamycin (KM) greater than AMK greater than HAPA-B. The IC50 (concentration which inhibited the response by 50%) of HAPA-B was 3.6 X 10(-3) g/ml. The neuromuscular blockade produced by HAPA-B was reversed by CaCl2, KCl or caffeine but not by neostigmine. D-Tubocurarine or MgCl2 augmented the neuromuscular effects of HAPA-B. Intramuscular (400 mg/kg) and intravenous (100 mg/kg) injections of HAPA-B did not affect the twitch response of gastrocnemius muscle to sciatic nerve stimulation in situ. Intravenous injection of 200 mg/kg caused death in some rats and depression of the twitch response in others. Intravenous AMK produced no significant effect on the twitch response at 50 mg/kg and caused death at 100 mg/kg. GM and SM caused death or significant degree of depression of the twitch response at intravenous doses of 50 mg/kg. In experiments of intravenous drug infusion for 60 minutes, the twitch response was depressed by HAPA-B at 400 mg/kg/hr and by AMK at 200 and 400 mg/kg/hr. In conclusion, HAPA-B has a neuromuscular blocking action presumably at the nerve terminal. However, its action was the weakest among the aminoglycoside antibiotics tested.
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PMID:[The neuromuscular blocking activity of isepamicin sulfate (HAPA-B) compared with other aminoglycoside antibiotics]. 358 26

(+)-Tubocurarine (TC) decreases the probability that the protozoan, Stentor coeruleus Ehrenberg, will contract in response to mechanical stimulation, because it selectively depresses mechanoreceptor currents. Resting membrane properties and action potentials are not significantly altered by the drug. Stentor incubated in media containing radioactively labelled TC (TC*) retain TC* after extensive washing despite a rather high apparent KD (19.7 mumol l-1). The incubation curve for TC* binding exhibits an initial exponential rise followed by a linear increase. Wash-out of bound TC* and elimination of the exponential component of the incubation curve is observed if the TC* incubation is followed by a 5-s exposure to 8% urea; therefore, the exponential component represents a reversible binding process. TC* binding in the exponential component is highly correlated (r less than -0.96) with the depression in receptor current and response probability when incubation time, drug concentration and drug (gallamine, TC, decamethonium and succinylcholine) are varied. These correlations suggest that the exponential binding is to functional mechanoreceptors. Mechanoreceptor currents are decreased by hyperpolarization and increased by depolarization, indicating that the mechanoreceptor channel is voltage-dependent. At hyperpolarized potentials the channels are in a form (the U form) which cannot be opened by mechanical stimulation; at depolarized potentials they are in a form (the R form) which can be opened. TC appears to bind to the U form with higher affinity than to the R form, since depolarization reduces the amount of bound TC* and relieves the depression of mechanoreceptor current produced by TC.
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PMID:The mechanism of tubocurarine action on mechanoreceptor channels in the protozoan Stentor coeruleus. 406 99

1. By the use of microiontophoretic techniques, quantitative estimates were obtained of the depressant effects of gamma-aminobutyric acid (GABA) on single feline cortical neurones.2. Picrotoxin, bicuculline, strychnine, (+)-tubocurarine, penicillin and leptazol were also applied microiontophoretically to single neurones. Sequential GABA applications were made before, during and after the microiontophoresis of these substances and any effects on the time course of the GABA depression were measured as an estimate of antagonism or potentiation of GABA.3. (+)-Tubocurarine was found to be a potent GABA antagonist. Picrotoxin and bicuculline were rather less potent and strychnine and penicillin only weakly active as GABA antagonists. Leptazol appeared to be inactive against GABA depressions.4. In addition, bicuculline and strychnine were found to be capable of potentiating the depressant action of GABA. This property was not shared by the other substances studied.5. All the substances studied produced changes in neuronal firing rate that did not correlate with GABA antagonism.6. In conclusion, several potent convulsants have been shown to be capable of GABA antagonism. It is not yet clear that this effect, rather than a direct effect on neuronal excitability, is the prime mechanism behind their convulsant properties.
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PMID:A comparative study of some convulsant substances as gamma-aminobutyric acid antagonists in the feline cerebral cortex. 415 Jul 64

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