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)

Dantrolene sodium is a muscle relaxant used in the treatment of spasticity. It has been shown to interfere with calcium release from the sarcoplasmic reticulum and thus to inhibit excitation--contraction coupling. The effect of dantrolene sodium on the twitch tension of the tibialis anterior muscle of the rat was measured after 2 mg/kg i.v. or 25 mg/kg orally. Plasma concentrations were estimated at maximum twitch depression and during recovery from the block. In a separate series of experiments the half-life of labelled dantrolene sodium was measured in blood plasma, skeletal muscle and heart muscle of rats. Dantrolene sodium 2 mg/kg i.v. gave a maximal block of approximately 47%, the mean dantrolene sodium concentration was then 5.8 microgram/ml. A half-life for distribution of 1.1 min and an elimination half-life of 31 min after intravenous administration were observed, elimination rate constants in skeletal and heart muscle were comparable. Recovery from the block went much slower, the half-time of the process being approximately 80 min. Dantrolene sodium 25 mg/kg orally gave a maximal block of approximately 38% at a mean plasma concentration of 3.6 microgram/ml after 14 min. The recovery was again very slow. These experiments demonstrated that dantrolene sodium acts according to a two-compartment pharmacokinetic model. There was a discrepancy between duration of effect and plasma concentration of dantrolene sodium in the rat. This suggests that the receptor for dantrolene sodium is not located in the central compartment.
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PMID:The effect of dantrolene sodium on rat skeletal muscle in relation to the plasma concentration. 42 31

Dantrolene sodium (Dantrium) is a skeletal muscle relaxant, unique in that it acts on the muscle itself. It should be considered for use in patients with skeletal muscle spasticity who are in a stable neurological state. After careful adjustment of the dose, a substantial number of such patients will experience one or more of the following benefits: (1) a reduction in pain, (2) an increased ability to make use of residual motor function, (3) a reduction in the level of nursing care required, (4) an increased ability to utilize devices, and (5) an increased ability to participate in rehabilitation. The drug should not be used when reduced spasticity will decrease functional ability. The adverse effects generally are transient; some are the result of central nervous system depression.
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PMID:Evaluation of a muscle relaxant: dantrolene sodium (Dantrium). 108 67

Dantrolene sodium (DS) was investigated for its effects on cat soleus muscle contractile properties and motor nerve terminal activity in particular. DS, 0.1-1.5 mg/kg i.v., caused a dose-dependent depression of indirectly elicited contractile strength which was more pronounced at lower frequencies of stimulation. Maximum tetanic strength at frequencies of 10-400 Hz was depressed to a lesser degree than contractile responses evoked by lower frequencies of stimulation; the twitch/tetanus contraction ratios were reduced with increasing dose, primarily because of diminished twitch. DS was without effect on motor nerve terminals as evidenced by normal post-tetanic repetition in the nerves following DS administration. Post-tetanic potentiation became relatively larger in amplitude as contractile strength was diminished. These data suggest that DS depresses neuromuscular function at a site other than the neural apparatus at the neuromuscular junction.
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PMID:Dantrolene effects on neuromuscular function in cat soleus muscle. 114 11

1. The action of the skeletal muscle relaxant drug, dantrolene sodium, given intravenously, on the intrafusal fibres of the soleus muscle of the urethane-anaesthetized rat has been investigated. The experiments were made on functionally single spindle afferents and gamma fusimotor fibers isolated in dorsal and ventral roots respectively. 2. Dantrolene sodium was without effect on the discharge of primary and secondary afferents from the passive muscle spindle, nor were the dynamic indices of these endings affected. 3. Intrafusal muscle contraction was measured indirectly by means of the spindle afferent discharge. 4. The intrafusal muscle twitch contraction, as measured by means of the amplitude of the frequencygram, was depressed more slowly to a lesser extent than was the twitch of the extrafusal contraction. 5. Intrafusal contraction resulting from tetanic stimulation of the gamma fibre was depressed by dantrolene sodium to an extent dependent upon the stimulation frequency. At frequencies of 10, 25 and perhaps 50 Hz the depression was complete, that is, no afferent response was evoked; at 200 Hz stimulation, the depression was minimal (or non-existent). 6. For a muscle spindle primary ending under dynamic gamma activation dantrolene sodium caused a reduction of dynamic index whereas for the ending under static activation it caused an increase. 7. The significance of the findings in terms of the clinical use of the drug is considered.
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PMID:The effect of dantrolene sodium on intrafusal muscle fibres in the rat soleus muscle. 645 47

Rats, anaesthetized with urethane, were injected intravenously with dantrolene sodium in a vehicle of 5% mannitol taken to pH 10 with NaOH. The muscle relaxant action of dantrolene sodium was measured from the contractions of individual motor units of the extensor digitorum longus (EDL), soleus (SOL) and segmental tail (ST) muscles. Data were also collected from their parent whole muscle preparations. The depressant action of dantrolene sodium on the percentage-normalized amplitude of contraction of the individual motor units was greater than its effect on the whole muscle twitch amplitude, in all three muscles. The twitch amplitude of fast contracting motor units was significantly more reduced (P less than 0.001) by dantrolene sodium than was that of slow contracting motor units. Dantrolene sodium reduced the contraction time of all motor units. The effect of the drug on half-relaxation time varied within and between groups of motor units studied. The drug was confirmed to have a greater depressant action on the twitch contraction than on the fused tetanus of whole muscle. This was true also for single motor units. With tetanic stimulation the effect of dantrolene sodium was also dependent upon the motor unit type, fast or slow. A maximum depression of contractile tension occurred at a stimulation frequency of 64 Hz for fast EDL motor units whereas the maximum depression for ST slow units, the slowest units tested, was at a stimulation frequency of 14 Hz.
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PMID:The action of dantrolene sodium on individual fast and slow motor units of the rat anaesthetized with urethane. 670 95

1. Rats, anaesthetized with urethane, were injected intravenously with dantrolene sodium in a carrier solution of 5% mannitol taken to pH 10 with NaOH. This carrier solution itself was without effect on extrafusal muscle contraction. 2. Dantrolene sodium (5 mg/kg) had a greater depressant action on the twitch contraction of the fast extensor digitorum longus (EDL) muscle than on the slow soleus (SOL) muscle. The EDL twitch was depressed to 25.9% +/- 1.2% (mean + s.e. mean, n = 7) of control whereas the SOL twitch was depressed to 31.3% +/- 0.4% (n = 9). These values were significantly different at the P less than 0.001 level. 3. The twitch contraction time to peak was reduced by approximately 35% in both EDL and SOL by dantrolene sodium. However, the drug reduced the half relaxation time of SOL by approximately 30% but that of EDL was hardly affected. 4. The effect of dantrolene sodium on contractions elicited by repetitive stimulation was dependent upon the stimulation frequency. For the SOL muscle the greater depression was produced at a stimulation frequency of 25 Hz and for EDL at 75 Hz. The minimum of depression was produced for a full fused tetanus for both muscles. 5. The significance of these findings is discussed in terms of the action of dantrolene sodium on motor control in the intact animal.
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PMID:The action of dantrolene sodium on rat fast and slow muscle in vivo. 728 84

Dantrolene sodium, a muscle relaxant, does not have a clinically useful antagonist. The present study was undertaken to test the efficacies of germine monoacetate, 4-aminopyridine, neostigmine, and calcium chloride as possible agents for the reversal of the direct skeletal muscle depression produced by dantrolene sodium in the cat anesthetized with alpha-chloralose. Depression of the indirectly elicited twitch responses (0.1 Hz) of the tibialis anterior muscle by 25, 50, 75 and 84 per cent was produced by dantrolene, 0.16, 0.36, 0.88 and 1.13 mg/kg respectively; spontaneous recovery of twitch tension during the subsequent 30 min was negligible. After the 30-min observation period had elapsed, one of the reversal agents under study was given (iv) in divided doses at intervals of 10 min (five cats for each agent). Germine monoacetate (2 X 0.5 mg/kg) immediately reversed the dantrolene-induced twitch depression, with an over-shoot that persisted for an hour. 4-Aminopyridine (4 X 0.5 mg/kg) caused a steady but incomplete reversal to 17 per cent depression, 30 min after the last dose. Neostigmine (4 X 0.04 mg/kg) caused an immediate, but transient, reversal of the twitch depression, with overshoot. Calcium chloride (4 X 10 mg/kg) was without effect. It is concluded that germine monoacetate is the drug of choice for reversal of the muscle depression produced by dantrolene sodium in the cat.
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PMID:Reversal of dantrolene sodium-induced depression of skeletal muscle in the cat. 745 84

Dantrolene effectively treats malignant hyperthermia (MH) hut the current form, Dantrium, must be dissolved to a 0.33 mg/mL, pH 9.5 solution. This study describes lecithin-coated microcrystal formulations of sodium dantrolene (MC-NaD) and neutral dantrolene (MC-D) which reconstitute to 200 mg/mL within 1 min. In rats, the pharmacokinetics and pharmacodynamics of MC-NaD and Dantrium were similar: half-lives of 3.1 h, volume distributions of 0.54 and 0.59 L/kg, and 95% effective dose (ED95) values for depression of skeletal muscle twitch height (ED95T) of 2.6 +/- 0.7 and 2.8 +/- 0.5 mg/kg. In swine, the ED95T values for MC-NaD and Dantrium were also similar (2.8 +/- 0.4 vs 2.7 +/- 0.6 mg/kg), but MC-D and Dantrium were only similar at doses more than 2.5 mg/kg (ED95T: 3.5 +/- 0.4 vs 2.7 +/- 0.5 mg/kg). In susceptible swine, MC-NaD successfully treated five of six MH episodes and prevented MH in three of four swine. However, MC-NaD caused marked pulmonary hypertension in swine, while MC-D caused only a mild response that was eliminated by filtration. Likewise, MC-D caused no pulmonary response in dogs. These observations suggest that MC-D has potential to improve the treatment of MH.
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PMID:Intravenous lecithin-coated microcrystals of dantrolene are effective in the treatment of malignant hyperthermia: an investigation in rats, dogs, and swine. 861

The administration of intravenous dantrolene in a parturient susceptible to malignant hyperthermia has been associated with post partum uterine atony. We examined the effect of dantrolene sodium for injection (Dantrium Intravenous) on spontaneous contractility of uterine smooth muscle from women in term pregnancy in an isolated preparation. Dantrolene sodium for injection at 5 microg/ml and 10 microg/ml had no effect on the spontaneous contractility of the uterine muscle preparations. At a cumulative concentration of 20 microg/ml, a mild depression (16 +/- 14%) in the frequency of spontaneous contractions was noted. However, a similar depression in the muscle preparations treated with mannitol suggests that the depression observed with the dantrolene was likely due to the mannitol that was included in the dantrolene formulation rather than to dantrolene sodium itself. We conclude that dantrolene sodium has no effect on the spontaneous contractility of uterine smooth muscle. The depression of uterine muscle activity observed with dantrolene for injection appears attributable to the mannitol.
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PMID:Effect of dantrolene sodium on contractility of isolated human uterine muscle. 1563 10