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. alpha-Bungarotoxin isolated from the venom of Bungarus multicinctus was acetylated with [(3)H] acetic anhydride and N-[(3)H] acetyl imidazole. Tri-N-acetyl and hexa-N-acetyl derivatives were obtained from the former, and N,O-di, N,N,O-tri and N,N,N,O-tetraacetyl derivatives from the latter reaction, respectively.2. There were parallel decreases in both neuromuscular blocking action in the phrenic nerve-diaphragm preparation of rats and depression of acetylcholine response of the rectus abdominis muscle of frogs with increased acetylation. Also, a parallel but greater decrease of toxicity in mice was found.3. N,O-Di and N,N,O-triacetyl toxins were localized mostly in the motor endplate region of the rat diaphragm, whereas a slight nonspecific binding along the whole muscle fibre in addition to the peak in the endplate region was observed with N,N,N,O-tetraacetyl and tri-N-acetyl toxins. In contrast, there was a marked nonspecific binding with hexa-N-acetyl toxin and no peak was observed at the endplate zone.4. The specific binding was saturable and irreversible. The number of toxin-receptive sites in one endplate was 1.9-2.2 x 10(7) for all of the labelled toxins irrespective of their potency.5. (+)-Tubocurarine protected effectively against the binding as well as the irreversible neuromuscular blocking effect of the toxins.6. Denervation of the rat diaphragm caused an increase of toxin-receptive sites beginning from the endplate zone at 1-2 days and then along the whole muscle fibre, reaching the maximum at about 18 days. The total receptive sites increased by about 30-fold.7. The significance of the findings is discussed and it is concluded that N,O-di and N,N,O-tri-[(3)H] acetyl alpha-bungarotoxins are specific and irreversible labelling agents for the cholinergic receptors of skeletal muscle.
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PMID:N,O-di and N,N,O-tri ( 3 H) acetyl -bungarotoxins as specific labelling agents of cholinergic receptors. 471 15

The in vivo cat soleus and gastrocnemius muscles were used to compare isometric contraction strength and the train-of-four (T4) response (2 Hz for 2 s) of two muscle types (fast and slow) during onset of competitive neuromuscular blockade in order to determine the extent of the correlation between twitch depression and T4 fade. Prior to drug administration the muscles that were studied differed significantly in that the T4 ratio was 1.0 in the gastrocnemius and only 0.87 in the soleus. Three competitive neuromuscular-blocking agents were compared: d-tubocurarine, pancuronium, and vecuronium. d-Tubocurarine was found to produce a close correlation between the degrees of twitch strength depression and T4 for both muscles. However, these muscles demonstrated significantly different ED50 values (105 micrograms/kg for gastrocnemius, 150 micrograms/kg for soleus). Pancuronium also produced a similar relationship between twitch strength depression and T4 decrement for each muscle. In this case, however, there was little difference in their ED50 values for twitch depression (11.5 micrograms/kg for gastrocnemius, 13 micrograms/kg for soleus). The effects of vecuronium were quite different from the other two muscle relaxants. Although vecuronium produced a comparable correlation between twitch tension and T4 fade in fast muscle, no such relationship was found to exist in slow muscle. Even when the twitch strength was blocked to 18% of control, the soleus T4 response was depressed to only 75% of control. These results highlight major differences among competitive neuromuscular-blocking agents and suggest multiple sites of action.
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PMID:Characterization of the train-of-four response in fast and slow muscles: effect of d-tubocurarine, pancuronium, and vecuronium. 613 67

In vitro experiments on the rat phrenic nerve-hemidiaphragm preparation, stimulated directly or indirectly with supramaximal impulses at 0.1 Hz revealed that pethidine in concentrations greater than 5 micrograms ml-1 caused a rapid increase of the twitch. This was maximal (60% increase during direct and 70% increase during indirect stimulation) with pethidine 75 micrograms ml-1. With concentrations of pethidine greater than 40 micrograms ml-1, the initial increase was followed by a slowly developing inhibition of the twitch (50% depression with 46.0 and 50.4 micrograms ml-1 during direct and indirect stimulation, respectively). Droperidol caused no increase in twitch, but it depressed the twitch by 50% at concentrations of 9.8 and 6.9 micrograms ml-1 during direct and indirect stimulation, respectively. The increase in twitch produced by pethidine was augmented by 4-aminopyridine and inhibited by verapamil during both direct and indirect stimulation. Tubocurarine antagonized the augmentation of the twitch by pethidine only during indirect stimulation. The pethidine- and droperidol-induced inhibition of the twitch could be reversed by washout, but it was not antagonized by neostigmine or 4-aminopyridine. The inhibitory effect of pethidine and droperidol were additive. Sub-effective inhibitory concentrations of pethidine and droperidol, and those of tubocurarine, pancuronium and suxamethonium, independently of the sequence of their administration, mutually increased the myoneural effects of one another. The resulting twitch depression could be reversed by washout. The inhibition caused by the combination of pethidine with tubocurarine or pancuronium was partially antagonized by neostigmine or 4-aminopyridine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myoneural effects of pethidine and droperidol. 669 80

Cutaneous pectoris muscles of Rana pipiens were transected distal to the innervated region. Within 10 min, membrane potentials (Em's) of -33 +/- 2.5 mV and end-plate potentials (3-15 mV) were recorded unaccompanied by muscle action potentials or twitch. The fall in Em was associated with a net loss of [K+]i and a net gain of [Na+]i. Although input resistance fell by 50% and the space constant was slightly reduced in the transected muscle fibers, end-plates could be adequately voltage-clamped with two microelectrodes. End-plate currents (e.p.c.s) with rise times of 350 to 700 musec were recorded as a function of holding potential (Vm). The current-voltage relationship of peak e.p.c.s over the range of -70 to +20 mV was linear and the reversal potential (-6.6 +/- 2.2 mV) was the same as that found for intact muscle fibers. The decay phase of e.p.c.s could be described as a single exponential at all Vm's and had a voltage and temperature dependence similar to that described for e.p.c.s of glycerol-treated muscles. Tubocurarine (0.3 microM) caused a significant decrease in the time constant (tau) of e.p.c. decay and e.p.c. amplitude. The depression of e.p.c. amplitude by tubocurarine was reversed by 4-aminopyridine while the decrease of tau was not. Atropine (10(-4) M) caused a monotonic shortening of e.p.c.s at a Vm of -90 mV but e.p.c.s recorded at +50 mV were biphasic. Lidocaine, a quaternary nitrogen analog of lidocaine (QX314), lobeline and hexafluorenium were studied also in transected muscle and their effects on the parameters of e.p.c. are described. Both lobeline (50 microM) and hexafluorenium caused a decrease of tau and eliminated the voltage dependence of tau at negative Vm's. The transected muscle can be used for the study of conductance kinetics of end-plate and for the study of drug action uncomplicated by the presence of other drugs of Mg++ to eliminate contraction.
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PMID:Characterization of end-plate conductance in transected frog muscle: modification by drugs. 696 98

We compared the cardiovascular and neuromuscular effects of Org NC 45 with those of pancuronium, metocurine, and d-tubocurarine in six dogs anesthetized with halothane. The ED90 (dose of drug which produced a 90% depression of twitch tension) of Org NC 45, pancuronium, metocurine, and d-tubocurarine was 14 +/- 3, 22 +/- 3, 63 +/- 19, and 130 +/- 19 micrograms/kg, respectively. All subsequent neuromuscular and cardiovascular effects were determined from a dose equal to 3 times the ED90 of muscle relaxant. Org NC 45, pancuronium, metocurine, and d-tubocurarine produced a neuromuscular blockade with a during (time from relaxant administration until recovery 50% of the original twitch tension) of 42 +/- 2, 108 +/- 10, 109 +/- 21, and 100 +/- 19 minutes, respectively. Org NC 45 caused no significant cardiovascular changes. Pancuronium increased heart rate, mean arterial blood pressure, cardiac output, and pulmonary wedge pressure, and it decreased systemic vascular resistance (p less than 0.05). Although metocurine also increased heart rate and cardiac output (p less than 0.05), mean arterial blood pressure and pulmonary wedge pressure did not change. d-Tubocurarine decreased all cardiovascular parameters except heart rate which increased significantly (p less than 0.05). We conclude that Org NC 45 produces a neuromuscular blockade of shorter duration with fewer cardiovascular changes than that of pancuronium, metocurine, or d-tubocurarine.
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PMID:Cardiovascular and neuromuscular effects of Org NC 45, pancuronium, metocurine, and d-tubocurarine in dogs. 718 62

An isolated, blood-perfused phrenic nerve-diaphragm preparation of the dog was developed for pharmacological investigation. A hemi-diaphragm with the ipsi-lateral phrenic nerve intact was excised from a dog anesthetized with pentobarbital sodium and was perfused with arterial blood from a donor dog through the phrenic artery. This preparation maintained its tone and response in good condition for 10 hr without any deterioration of twitch tension. Effects of succinylcholine, d-tubocurarine, decamethonium, and gallamine on twitch tension and blood flow of this preparation were studied. Drugs were injected into the phrenic artery. All four compounds produced a dose-dependent depression of twitch tension elicited by indirect stimulation applied to the phrenic nerve without any depression in the tension elicited by direct stimulation applied to the muscle. The ratios of the potency to produce a 50% depression in twitch tension elicited by indirect stimulation among succinylcholine, decamethonium, d-tubocurarine, and gallamine were roughly 1:1/3:1/3:1/30 on a weight (mg) basis. d-Tubocurarine produced a dose-dependent increase in blood flow. Other compounds did not cause significant changes in blood flow. The increase in blood flow produced by d-tubocurarine was markedly inhibited by diphenhydramine, which suggested histamine release by d-tubocurarine.
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PMID:Isolated, blood-perfused phrenic nerve-diaphragm preparation of the dog: description of a new method and effects of neuromuscular blocking agents on twitch tension and blood flow. 726 94

Repetitive discharges recorded from the ventral root and from the gastrocnemius muscle in response to single motor nerve shocks applied close to the muscle after injection of edrophonium, neostigmine or ambenonium were studied in cats anaesthetized with chloralose. Two closely spaced volleys with an interval of 1 to 5 msec between them produced more repetitive firing than did a single shock. With longer intervals, the repetitive firing was not potentiated by the second volley. All frequencies of tetanic stimulation depressed the repetitive firing and, for successive stimuli to produce a degree of repetitive firing equivalent to the first, it was necessary to stimulate at frequencies below 2 shocks/sec. With stimulation frequencies higher than 100 shocks/sec, repetitive firing did not occur unless the duration of the tetanus was shorter than about 30 msec when slight repetition followed the last stimulus of the train. With stimulation frequencies of 100 down to 20 shocks/sec, repetitive firing was produced only by the first volley of the tetanus. Subsequent nerve action potentials of the tetanus occurring during the repetitive firing in the nerve following the first volley were partially extinguished by collision with the back discharge. This effect contributed to the waning tetanus, which is characteristic of treatment with an anticholinesterase, but the main depression of tetanic contractions appeared to be a consequence of depolarization block through accumulating acetylcholine. Tubocurarine and benzoquinonium reversed the initial "extinction" phase of the depressed tetani by abolishing the repetitive discharge in the nerve and in larger doses reversed the secondary depressant phase presumably by reducing the excessive end-plate depolarization. The results are discussed in relation to the hypothesis that anticholinesterases may effect transmission by acting at three sites at the neuromuscular junction-on acetylcholinesterase, at the motor nerve ending and at the motor end-plate-and that reaction at any one site may be augmented by the production of reverberating activity across the junction.
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PMID:Studies on the repetitive discharges evoked in motor nerve and skeletal muscle after injection of anticholinesterase drugs. 1397 50


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