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PubMed2002

Abnormal cortical mechanisms of voluntary muscle relaxation in patients with writer's cramp: an fMRI study.

Although it is hypothesized that there is abnormal motor inhibition in patients with dystonia, the question remains as to whether the mechanism related to motor inhibition is specifically impaired. The objective of the present study was to clarify the possible abnormalities of the mechanisms underlying voluntary muscle relaxation during motor preparation and execution in patients with writer's cramp, using event-related functional MRI. Eight patients with writer's cramp and 12 age-matched control subjects participated in the study. Two motor tasks were employed as an experimental paradigm. In the relaxation task, subjects were asked to hold their right wrist in the horizontal plane by maintaining moderate contraction of wrist extensor muscles in the premotor phase; they relaxed those muscles voluntarily just once during each fMRI scanning session. In the contraction task, subjects extended the right wrist voluntarily from the same premotor state as for the relaxation task. Five axial images covering the primary sensorimotor cortex (SMC) and supplementary motor area (SMA) were obtained once every second. Activated volumes in the left SMC and the SMA were significantly reduced in patients for both muscle relaxation and contraction tasks. These data suggest that there is impaired activation in both SMC and SMA in voluntary muscle relaxation and contraction in patients with writer's cramp. This implies that abnormalities of both inhibitory and excitatory mechanisms in motor cortices might play a role in the pathophysiology of focal dystonia.

Adult↗
PubMed1985

Hindered muscle relaxation in spasticity: experimental evidence suggesting a possible pathophysiological mechanism.

In ten spastic patients and in an equal number of healthy controls, the relaxation phase occurring at the end of an isotonic voluntary contraction has been studied on soleus muscle using EMG and H-reflex methods. In the spastic group, the duration of motor unit-decruitment was consistently prolonged (from two to six times the control values). Moreover, the decrease in the excitability of the H-reflex arc, which normally accompanies the end of muscle contraction was delayed in time, reduced in amplitude or in some cases even absent. As a rule, patients in whom such release-associated inhibition (RAI) was lacking or severely reduced exhibited the longest motor unit-decruitment times, due to the interference of sustained clonic sequences. It is proposed that a lowered effectiveness of RAI might explain the clonic activity which frequently hinders voluntary muscle relaxation in spasticity.

Adult↗
PubMed2002

Anionic cyclophanes as potential reversal agents of muscle relaxants by chemical chelation.

A series of carboxyl-containing cyclophanes have been designed and synthesised as chemical chelators (or host molecules) of cationic muscle relaxant drugs (or guest molecules). Three of these cyclophane derivatives, 1-3, have been shown by NMR to form 1:1 complexes with the muscle relaxants pancuronium, and gallamine, in D(2)O, with association constants up to 10(4) M(-1). When tested in an in vitro chick biventer muscle preparation, the cyclophanes reversed the neuromuscular block induced by pancuronium and gallamine, with having the most effective reversal against pancuronium (EC(50) 40 microM.

Animals↗
PubMed1985

Desensitization of beta-adrenergic receptor-mediated vascular smooth muscle relaxation.

Responsiveness to catecholamines may be blunted after prolonged exposure to an agonist; this phenomenon, termed desensitization, is often mediated by receptor down-regulation. beta-Adrenergic receptors mediate relaxation of vascular smooth muscle. We have examined the possibility that this response may be desensitized after prolonged exposure to increased concentrations of epinephrine. Rats were treated with epinephrine infusions (300 micrograms/kg/hr from a minipump) for 7 days and had levels of plasma epinephrine 70-fold greater than those of controls. The mesenteric artery rings from the epinephrine-treated rats contracted normally when exposed to serotonin; however, the extent of relaxation promoted by the beta-adrenergic agonist isoproterenol was blunted (86 +/- 4 vs. 43 +/- 9%; p less than 0.05). Acetylcholine and nitroglycerine, which may act through a cyclic GMP mechanism, caused virtually identical relaxation responses in both control and epinephrine-treated groups. To determine the mechanism for the loss in responsiveness to isoproterenol, we measured adrenergic receptors in individual mesenteric arteries using [125I]cyanopindolol. Specific binding of [125I]cyanopindolol was found to have the expected characteristics of interaction with beta receptors. There was no difference in the number of beta-adrenergic receptors between control and epinephrine-treated animals (24 +/- 5 vs. 26 +/- 6 fmol/mg of protein), although there was significantly marked down-regulation of beta-adrenergic receptors in hearts (23 +/- 2 vs. 10 +/- 1 fmol/mg of protein; p less than 0.001) and lungs (172 +/- 29 vs. 76 +/- 7 fmol/mg of protein; p less than 0.01) in the same rats. The ability of isoproterenol to stimulate cyclic AMP production in the mesenteric arteries from the two groups was not significantly different (20.3 +/- 3.5 vs. 23.8 +/- 4.7 pmol of cAMP/mg of protein/2 min). Furthermore, mesenteric artery relaxation was found to be decreased in response to the cyclic AMP analogue dibutyryl cyclic AMP (45 +/- 2.0 vs. 28 +/- 2.0%; p less than 0.001) in the epinephrine-infused rats. These data suggest that the desensitization of beta-adrenergic receptor-mediated smooth muscle relaxation may be caused by a mechanism distal to cyclic AMP production.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Progressive muscle relaxation and restricted environmental stimulation therapy for chronic tension headache: a pilot study.

Thirty-one patients suffering from chronic tension headache participated in one of four procedures, each of which comprised two one-and-one-half hour sessions per week for 4 weeks. The conditions were: Chamber/Control (both weekly sessions lying on a bed in a dimly-lit room), and three active treatment procedures: Chamber/Tank, one session as above, the other floating in a dark, silent REST tank; Chamber/Relaxation, one as above, one doing progressive muscle relaxation exercises; and Tank/Relaxation, one session floating and one doing progressive muscle relaxation. By 6 months after the end of treatment, complete data had been obtained from 20 subjects. There was a significant overall decrease in headache reports; the active treatment groups collapsed improved significantly more than the control group. At the 6-month followup, the treatment groups showed continuing improvement (57% over end of treatment for the Tank-Relaxation group and a mean of 25% for the other two), whereas the control group had deteriorated by 34% since end of treatment. Clinical improvements were comparable to those of more time- and effort-consuming relaxation therapies, and confirm the usefulness of REST as a long-lasting and versatile treatment in behavioral health.

Adult↗
PubMed1993

Use of a new syringe pump (Springfusor) for muscle relaxant infusion.

A new spring-driven syringe pump (Springfusor 10, Go Medical Industries, Subiaco, W.A.) was evaluated for infusion of muscle relaxants in 50 surgical cases. After an initial bolus dose, atracurium was given at a rate of 25 to 37.5 mg/hour and vecuronium at a rate of 4 to 6 mg/hour. The mean infusion rate was found to be 4% above the nominal rate of 5 ml/hour and the accuracy in all cases was within +/- 20%. The Springfusor was found to be rugged, cheap and easy to use. It lacks dose flexibility but is suitable for continuous background infusion of muscle relaxants during surgery.

Adult↗
PubMed2006

The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system.

Thiocolchicoside (TCC) is used clinically for its muscle relaxant, anti-inflammatory, and analgesic properties, and it has been shown to interact with gamma-aminobutyric acid (GABA) type A receptors (GABAARs) and strychnine-sensitive glycine receptors in the rat central nervous system. In contrast to a proposed agonistic action at these two types of inhibitory receptors, pharmacological evidence has shown that, under certain conditions, TCC manifests convulsant activity in animals and humans. We now show that the phasic and tonic GABAAR-mediated currents recorded from Purkinje cells and granule neurons, respectively, in parasagittal cerebellar slices from adult male rats were inhibited by TCC in a concentration-dependent manner. The median inhibitory concentrations of TCC for these effects were approximately 0.15 and approximately 0.9 microM, respectively. TCC did not potentiate GABABR-mediated currents in hippocampal slices, suggesting that its muscle relaxant action is not mediated by GABABRs. Intraperitoneal injection of TCC in rats either alone or in combination with negative modulators of GABAergic transmission revealed convulsant and proconvulsant actions of this drug. Our data, consistent with clinical observations of the epileptogenic effect of this compound, suggest that TCC is a potent competitive antagonist of GABAAR function.

Animals↗
PubMed2003

Indanylidenes. 1. Design and synthesis of (E)-2-(4,6-difluoro-1-indanylidene)acetamide, a potent, centrally acting muscle relaxant with antiinflammatory and analgesic activity.

The design of rigid cyclic analogues derived from cinnamamide 1, (E)-N-cyclopropyl-3-(3-fluorophenyl)prop-2-enamide, and beta-methylcinnamamide 2, (E)-N-cyclopropyl-3-(3-fluorophenyl)but-2-enamide, has led to the discovery of the potent, centrally acting muscle relaxant (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 17. Compound 17 also possesses potent antiinflammatory and analgesic activity. This paper describes the synthesis and the muscle relaxant, antiinflammatory, and analgesic structure-activity relationships of 17 and 67 of its analogues. Compound 17 has been taken into phase I clinical trials.

Acetamides↗
PubMed1986

A pharmacokinetic explanation for increasing recovery time following larger or repeated doses of nondepolarizing muscle relaxants.

The authors used pharmacokinetic and pharmacodynamic modeling to explain the time course of neuromuscular blockade following single or multiple doses of three nondepolarizing muscle relaxants. Published and unpublished pharmacokinetic and pharmacodynamic data for 13 normal subjects were used to simulate the duration of neuromuscular blockade (time from administration of the muscle relaxant to 25% recovery of control twitch tension) following six successive doses of atracurium (150-400 micrograms/kg initially, followed by 100 micrograms/kg), vecuronium, or pancuronium (30-80 micrograms/kg initially, followed by 20 micrograms/kg). With atracurium, duration of action was similar for the second and sixth doses, regardless of the initial dose. With vecuronium (initial doses of 30-80 micrograms/kg) and pancuronium (initial doses of 30-60 micrograms/kg), duration of action was longer after the sixth dose than after the second; with larger initial doses of pancuronium (70 and 80 micrograms/kg), duration of action was similar following the second and sixth doses. The authors also determined two recovery times (time for twitch tension to recover from 5-25% and from 25-75% of control value) for varying single doses of atracurium, vecuronium, or pancuronium. When the dose of atracurium was increased from 200 to 400 micrograms/kg, neither recovery time increased. When the dose of vecuronium was increased from 40 to 80 micrograms/kg, 5-25% recovery time increased from 6.0 +/- 2.5 min to 8.8 +/- 4.0 min (mean +/- SD) and 25-75% recovery time increased from 8.7 +/- 4.3 min to 12.6 +/- 4.4 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Role of cyclic GMP in airway smooth muscle relaxation.

The evidence in favor of a role for cyclic GMP as a mediator of relaxation in airway smooth muscle is reviewed. All of the criteria usually used to decide whether a cyclic nucleotide is the mediator of a particular response appear to have been satisfied, at least to some extent, for a causal relationship between cyclic GMP elevation and relaxation of airway smooth muscle.

Animals↗
PubMed1983

Five non-depolarizing muscle relaxants in precurarization.

Five different non-depolarizing muscle relaxants and a control solution of saline were studied as precurarization agents. Two hundred and twenty-two surgical patients (ASA I-II) were allocated in a double-blind fashion to one of the following groups: d-tubocurarine 0.05 mg/kg, alcuronium 0.03 mg/kg, pancuronium 0.01 mg/kg, gallamine 0.25 mg/kg, ORG NC-45 (vecuronium) 0.01 mg/kg and saline solution 0.005 ml/kg. Pretreatment was performed 4 min before administering a 1.5 mg/kg bolus of succinylcholine (SCh). Fasciculations, intubation conditions, duration of neuromuscular blockade after SCh, serum potassium changes and postoperative myalgias (in 60 patients) were recorded. All the drugs studied prevented fasciculations significantly (P less than 0.05) more than in the control group. d-Tubocurarine and alcuronium were superior to the others in this respect. Intubation conditions were best in the control and pancuronium groups, but there was no significant difference between the pancuronium and d-tubocurarine or between the d-tubocurarine and alcuronium groups. Pancuronium pretreatment prolonged the SCh block significantly, whereas other agents shortened the duration of the SCh block. The antagonism of the SCh block apparently also affected intubation conditions, although intubation remained satisfactory. A statistically significant rise in serum potassium level was measured only in the control and pancuronium groups. In the control and pancuronium groups, four patients out of 10 had postoperative myalgias, whereas in the other groups only one or none out of 10 had them (0/10 vs. 4/10; 0.10 greater than P greater than 0.05). In conclusion, d-tubocurarine and alcuronium seem to have advantages over pancuronium, ORG NC-45 and gallamine for precurarization.

Adolescent↗
PubMed1996

[New muscle relaxants].

Mivacurium is a short-acting nondepolarising muscle relaxant of the benzylisoquinoline type undergoing rapid breakdown by plasma cholinesterase. With 2.5 fold ED95, tracheal intubation can be accomplished within 2-3 min following injection. The ensuing DUR 25% (i.e. time from injection to 25% recovery of control twitch tension) is three times as long as with succinylcholine and about half as long as with equipotent doses of atracurium and vecuronium. The principal side effects of mivacurium are facial flushing and a transient fall in blood pressure due to a moderate histamine release following doses of 3-4 times the ED95. In patients with end stage liver or renal disease as well as in patients with atypical plasma cholinesterase the duration of action of mivacurium is prolonged. Rocuronium is a steroidal non-depolarising neuromuscular blocking agent chemically related to vecuronium. Compared with the latter, rocuronium is less potent, has a shorter onset of action, and no cumulative effects. Adequate intubating conditions are achieved within 60 to 90 s after i.v. injection of twice the ED95. Its elimination from the blood occurs primarily via liver uptake, while renal elimination is about 10 to 30%. Slight vagolytic effects are reported following injection of 0.6 mg/kg rocuronium, while histamine release is unlikely to occur. Atracurium is a mixture of ten stereoisomers. One of them, cis-atracurium, is five times as potent as the chiral mixture while having a similar pharmacodynamic and kinetic profile. It does not cause significant histamine release or clinically relevant cardiovascular effects at doses up to 8 times the ED95. Laudanosine release seems to be less with cis-atracurium than with atracurium.

Androstanols↗
PubMed2000

Skeletal muscle relaxants: pharmacodynamics and pharmacokinetics in different patient groups.

Muscle relaxants can be safely administered during anaesthesia, providing the basic pharmacodynamic and pharmacokinetic characteristics of the compounds together with the physiological status of the patient are known. In this review the pharmacodynamics and pharmacokinetics of the neuromuscular blocking agents are discussed and related to the physical health or disease state of groups of patients.

Adjuvants, Anesthesia↗
PubMed2004

[Feedback control of muscle relaxation with a varying on-off controller using cisatracurium].

BACKGROUND: Under clinical conditions constant neuromuscular blockade can also be maintained by a simple closed-loop system. However, delayed onset time, non-linearity of the dose-response curve and different sensitivity to muscle relaxants for each patient are limiting factors. METHODS: In 20 patients who underwent elective surgical procedures under continuous propofol/alfentanil anaesthesia and relaxation with cisatracurium, the maintenance of an electromyographically controlled cisatracurium block of 90% was achieved by a varying on-off control system. Using an own computer-aided measuring device, the course of the neuromuscular blockade and deviations from the desired neuromuscular block were registered. RESULTS: Over a period of 64.2+/-14.0 min, neuromuscular block could be controlled on average at a T(1)-level of 10% (90% block). The mean error of the deviation of the obtained neuromuscular blockade from the set-point was -1.6+/-0.9% on average. To maintain this neuromuscular blockade, a dose rate of 1.4+/-0.9 micro g x kg(-1) x min(-1) cisatracurium was necessary. CONCLUSIONS: It can be concluded that a simple closed-loop system allows the safe use of the intermediate term muscle relaxant cisatracurium for the performance of surgical procedures.

Adult↗