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PubMed2004

An investigation of non-depolarizing muscle relaxants on embryonic development in cultured rat embryos.

BACKGROUND AND OBJECTIVE: We have investigated the toxic and teratogenic effects of certain non-depolarizing muscle relaxants on embryonic development in cultured rat embryos. METHODS: Rat embryos of 9.5 days were explanted and cultured in vitro for 48 h in rat serum. Whole rat serum was used as a culture medium for the control group while different concentrations of atracurium, cis-atracurium, rocuronium and mivacurium were added to rat serum for the experimental groups. Dose-dependent effects of these agents on embryonic developmental parameters were compared using morphological and biochemical methods. Each embryo was evaluated for the presence of any malformations. RESULTS: When compared to the control embryos, the muscle relaxants significantly decreased all growth and developmental parameters dose dependently with an increase in overall dismorphology. Among these malformations, maxillary deformity was most frequently observed. These effects were observed in much lower doses with atracurium and cis-atracurium compared to those with rocuronium and mivacurium. CONCLUSIONS: Our results suggest that non-depolarizing muscle relaxants cause dose-dependent toxicity on rat embryos at concentrations much greater than those in clinical practice. Although, these agents seems to have a low potential for causing developmental toxicity during organogenesis, because of the lower toxic effects observed with rocuronium and mivacurium, these agents may be preferred when recurrent administrations are necessary for parturients.

Abnormalities, Drug-Induced↗
PubMed2001

The effect on intraocular pressure of tracheal intubation or laryngeal mask insertion during sevoflurane anaesthesia in children without the use of muscle relaxants.

BACKGROUND: We studied the effects of sevoflurane on intraocular pressure after induction in children undergoing either tracheal tube (TT) or laryngeal mask airway (LMA) insertion without a muscle relaxant METHODS: The study included 38 children. Anaesthesia was induced (8%) and maintained (3-4%) with sevoflurane in 100% O2. No muscle relaxant was used. A TT was inserted in group I (n=20), and an LMA in group II (n=18). IOPs were measured after induction, insertion of TT or LMA and at 1, 2 and 3 min thereafter. The heart rate, mean arterial pressures were also recorded. RESULTS: Intraocular pressures increased significantly in group I after TT (P < 0.01) and remained high until after 3 min. The pressures were similar in the LMA group at all measurements. CONCLUSION: Sevoflurane does not prevent the increase in IOP after intubation without muscle relaxants. LMA does not increase IOP in children after sevoflurane induction.

Anesthesia, Inhalation↗
PubMed1975

An electromyographic study of muscle relaxants in man.

Supramaximal paired stimuli were applied to the ulnar nerve, and the amplitude of the muscle action potential evoked in the abductor digiti minimi by the second member of the stimulus pair (test response) was compared with that evoked by the first component (conditioning response). The interval between the two components of the stimulus pair (the pair interval) was increased stepwise from 7 to 100 msec and a curve (recovery curve) was obtained by relating the changes in pair interval to the difference in amplitude of the test and conditioning responses. Alterations of the recovery curve (RC) during partial paralysis by muscle relaxants were investigated in healthy adult patients under the lightest plane of general anaesthesia. The control curve obtained in 32 subjects before the administration of a muscle relaxant drug was characterized by slight depressions at very short intervals of paired stimuli, followed by a slight potentiation at 20-100 msec. With non-depolarizing relaxants, RC altered to the characteristic pattern of potentiation at very short intervals of stimuli, followed by a notable depression at longer intervals. In depolarizing blocks with small doses of suxamethonium, the depression of RC at short intervals in the control was enhanced and the pattern of RC was different from that of non-depolarizing agents. When desensitization blocks were instigated by the i.v. administration of suxamethonium, the RC patterns were similar to those of competitive agents.

Action Potentials↗
PubMed1985

Excitability of reciprocal and recurrent inhibitory pathways after voluntary muscle relaxation in man.

We studied the potential contribution of postsynaptic mechanisms to the depression of reflex excitability which occurs immediately after a voluntary release from tonic muscle contraction. The excitability of the Soleus (Sol) motor pool was tested at rest and after voluntary muscle relaxation. In both cases the Sol H-reflex was conditioned by a single shock to the peroneal nerve, in order to activate the Ia interneurones (INs) mediating the reciprocal inhibition via a peripheral input, or by a short-lasting voluntary contraction of the Tibialis Anterior (TA) muscle, to activate the Ia INs via a central command. Changes in excitability of Renshaw cells were also tested at rest and after release, to assess the role of recurrent inhibition in the release-induced inhibition of the Sol H-reflex. It was demonstrated that: the excitability of the INs mediating the reciprocal inhibition was only slightly enhanced in comparison with resting conditions; the H-reflex of the antagonist muscle (TA) evoked after Sol release was not consistently facilitated with respect to rest; the command to contract the TA muscle reduced the H-reflex of the Sol muscle during rest but not after Sol release; recurrent inhibition did not increase its effect in the post-release period. Such features suggest that recurrent and reciprocal post-synaptic inhibitions do not play a major role in reducing the reflex excitability of a relaxing muscle; rather, the command to release prevents the reciprocal inhibitory effect which accompanies the contraction of the antagonist muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effects of centrally acting muscle relaxants on post-rotatory nystagmus in the rabbit.

1. The effects of some centrally acting muscle relaxants on the post-rotatory nystagmus induced by rotatory stimulation were investigated in the rabbit, to examine the action of the drugs on vestibular function. 2. Tolperisone-HCl (5-10 mg/kg, i.v.) and baclofen (1-3 mg/kg, i.v.) decreased the number of post-rotatory nystagmus beats dose-dependently, whereas mephenesin (40-80 mg/kg, i.v.) and diazepam (0.5-1.0 mg/kg, i.v.) prolonged it dose-dependently. 3. The inhibitory effects of tolperisone-HCl and baclofen may provide some suggestions as to the mechanisms and sites of actions of centrally acting muscle relaxants, while the significance of the prolonging action of mephenesin remains unclear. 4. The prolonging action of diazepam is discussed with reference to GABAergic mechanisms.

Animals↗
PubMed1983

Effects of progressive muscle relaxation and music on stress as measured by finger temperature response.

Measured the efficacy of music, progressive muscle relaxation, and a combination of both variables on tension reduction. Ss were three sections (N = 76) of an introductory music class. Each section received either sedative music (M), progressive muscle relaxation (PMR), or both (M + PMR) as treatment. Vasoconstriction, or finger temperature, was used to measure stress level prior to and after the intervention. All three groups evidenced significant increases in finger temperature. There was no significant difference among treatment groups, although the M + PMR group's mean increase was greater than the grand mean, while the M and PMR groups' increases were below the grand mean.

Adult↗
PubMed1976

Anticholinergic actions of steroid muscle relaxants.

The chronotropic effects of two new steroid muscle relaxants have been investigated. Each was compared individually with pancuronium bromide, using acetylcholine as an agonist on the isolated perfused rabbit heart. One of the drugs. Organon 6368, was very similar to pancuronium in its degree of antagonism to the bradycardia produced by acetylcholine and may therefore be a useful drug clinically. Dacuronium, on the other hand, would appear to have marked chronotropic effects at dose levels needed for adequate neuromuscular blockade and thus may be less useful.

Acetylcholine↗
PubMed1981

[Effects of afloqualone, a centrally acting muscle relaxant, on the sleep-wakefulness cycle in cats with chronically implanted electrodes (author's transl)].

The present study was carried out to elucidate whether or whether not afloqualone has a hypnotic action because of its similarity in chemical structure to methaqualone. In the sleep-wakefulness cycles during the 8-hour observation period (9:00-17:00), afloqualone increased the percentages of resting (REST) and slow wave light sleep (SWLS) stages at a dose of 25 mg/kg (p.o.), producing a moderate muscle relaxation. Even at a dose of 50 mg/kg (p.o.) where a marked muscle relaxation was produced, afloqualone had no influence on the percentage of slow wave deep sleep (SWDS) stage, though it increased the percentages of SWLS and decreased the percentages of awake (AWK), REST and fast wave sleep (FWS) stages. On the other hand, tolperisone . HCl, chlormezanone, methaqualone and pentobarbital . Na, used as the reference drugs, all increased the percentage of SWDS stage, but either decreased or had no effect on the percentages of the other four stages at pharmacologically effective doses. From these results it was concluded that afloqualone seems to be devoid of a hypnotic action and has different effects on the sleep-wakefulness cycle than those of both the hypnotics and the other muscle relaxants used.

Animals↗
PubMed1961

Centrally acting muscle relaxants in tetanus.

The anti-tetanus activity of a number of phenothiazine derivatives and other centrally acting muscle relaxants, such as mephenesin, dicyclopropyl ketoxime, 2-amino-6-methylbenzothiazole and meprobamate, has been determined in rabbits with experimental local tetanus. Structure-activity relationships were obtained for the phenothiazine derivatives and their anti-tetanus activity correlated with other central and peripheral properties. Both dicyclopropyl ketoxime and 2-amino-6-methyl-benzothiazole were twice as active as mephenesin. Meprobamate does not appear to be primarily a muscle relaxant of the mephenesin type.

Animals↗
PubMed2001

Nitric oxide-mediated corpus cavernosal smooth muscle relaxation is impaired in ageing and diabetes.

OBJECTIVE: To examine nitric-oxide (NO)-mediated relaxation in cavernosal smooth muscle in a rat model of diabetes, as previous experiments showed that HbA1c (an isoform of glycosylated haemoglobin and a marker of long-term diabetic control) impaired NO-mediated relaxation of normal corpus cavernosal tissue through the generation of superoxide anions. MATERIALS AND METHODS: Eight weeks after the induction of diabetes, male Wistar rats were killed and cavernosal tissue obtained. Strips were contracted with 1 micromol/L noradrenaline before applying acetylcholine or electrical field stimulation (EFS) or sodium nitroprusside (SNP). Relaxation responses were repeated in the presence of L-arginine (100 micromol/L), indomethacin (10 micromol/L) or superoxide dismutase (SOD, 120 IU/mL). Young and age-matched control animals were examined in the same way. RESULTS: Eight weeks of uncontrolled diabetes caused a significant impairment in mean relaxation responses to acetylcholine (P < 0.05) and to EFS (P < 0.05), but not to SNP, compared with young and age-matched controls, respectively. L-arginine, indomethacin and SOD had no significant effect on this impairment. Ageing caused a lesser but significant impairment in EFS-mediated cavernosal smooth muscle relaxation (P < 0.05). CONCLUSION: Diabetes impairs endothelial and neuronal NO-mediated cavernosal smooth muscle relaxation in rats in vitro. This effect is not mediated by an alteration in the intracellular action of NO, the availability of NO, superoxide anion inactivation of NO or the generation of constrictor prostanoids. It is possible that cholesterol or advanced glycation end products are responsible for the effect of diabetes on penile smooth function.

Acetylcholine↗
PubMed1989

The effect of smooth muscle relaxants working through different transduction mechanisms on the phorbol dibutyrate-induced contraction of the guinea-pig lung parenchymal strip: possible relevance for asthma.

It has been suggested that protein kinase C activation may have a role in the maintained, 'latch-bridge' phase of smooth muscle contraction. We have examined the effects of a range of smooth muscle relaxants on the maintained contraction produced in the guinea-pig parenchymal lung strip by the protein kinase C activator, 4 beta-phorbol dibutyrate (4 beta-PDBu). The maximum histamine contraction (produced by 10 microM) was used as a standard and the effects of the smooth muscle relaxants were also studied on this histamine-induced contraction. After 4 beta-PDBu, 1 microM, had produced contraction, enprofylline, forskolin and papaverine caused concentration-dependent relaxation, producing total reversal of the contraction, while prostaglandin E2 and prostacyclin caused a concentration-dependent relaxation but less than total reversal. The concentrations required for the effects on the phorbol ester contraction were 10 to 100-fold higher than were necessary for relaxation of the maximum contraction produced by histamine. Isoprenaline, 1 microM, a concentration which caused total reversal of the histamine-induced contraction, caused only 22% decrease of the phorbol dibutyrate-induced contraction and no further relaxation occurred with higher concentrations. Cromakalim--a potassium channel activator proposed as a therapy for nocturnal asthma--had virtually no effect on preparations pre-contracted with 4 beta-PDBu, 1 microM, or histamine, 10 microM, but caused about 70% and 20% reversal of the contraction produced by 3 microM histamine and 100 nM 4 beta-PDBu respectively. When single doses of the relaxants were administered before a series of doses of 4 beta-PDBu given cumulatively, enprofylline, 1 microM, and aminophylline, 100 microM and 1 microM, caused a moderate right-shift of the phorbol dibutyrate concentration-response curve, but isoprenaline, 1 microM, was less effective, while cromakalim had no discernible effect. These results are discussed in the light of suggestions that inappropriate activation of protein kinase C in smooth muscle cells, may contribute to the pathogenesis of the late phase of asthma.

Animals↗
PubMedDate not supplied

The detection and identification of quaternary nitrogen muscle relaxants in biological fluids and tissues by ion-trap LC-ESI-MS.

Quaternary nitrogen muscle relaxants pancuronium, rocuronium, vecuronium, gallamine, suxamethonium, mivacurium, and atracurium and its metabolites were extracted from whole blood and other biological fluids and tissues by using a solid-phase extraction procedure. The extracts were examined by using high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). The drugs were separated on a ODS column in a gradient of ammonium acetate buffer (pH 5.0) and acetonitrile. Full-scan mass spectra of the compounds showed molecular ions, and MS-MS spectra showed fragments typical of the particular compounds. LC-ESI-MS allowed an unequivocal differentiation of all muscle relaxants involved. The method was applied in a case of rocuronium and suxamethonium administration in a Caesarian section and in a case of intoxication by pancuronium injection. In both cases, the administered drugs could be detected and identified in the supplied samples.

Adult↗
PubMed2002

Change in length of relaxed muscle fascicles and tendons with knee and ankle movement in humans.

Ultrasonography was used to measure changes in length of muscle fascicles in relaxed human tibialis anterior and gastrocnemius during passively imposed changes in joint angle. Changes in the length of muscle fascicles were compared to changes in the length of the whole muscle-tendon units calculated from joint angles and anthropometric data. Relaxed muscle fascicles underwent much smaller changes in length than their muscle-tendon units. On average, muscle fascicles in tibialis anterior 'saw' 55 +/- 13 % (mean +/- S.D.) of the total change in muscle-tendon length. This indicates nearly half of the total change in muscle-tendon length was taken up by stretch of tendon. In gastrocnemius, which has relatively long tendons, only 27 +/- 9 % of the total change in muscle-tendon length was transmitted to muscle fascicles. Thus, the tendency for passive movement to be taken up by the tendon was greater for gastrocnemius than tibialis anterior (P = 0.002). For these muscles, the relatively large changes in tendon length across much of the physiological range of muscle-tendon lengths could not wholly be explained by tendon slackness, changes in fibre pennation, or stretch or contraction history of the muscle. Our data confirm that when joints are moved passively, length changes 'seen' by muscle fascicles can be much less than changes in the distance between muscle origin and insertion. This occurs because tendons undergo significant changes in length, even at very low forces.

Adult↗
PubMed1983

[Muscle-relaxant effects of intravenously administered micronomicin].

Pharmacological effects, mainly on its muscle-relaxant of micronomicin (MCR) were studied. Intravenous infusion of MCR at a dose of 20 mg/kg/hour did not influence on both respiration rate and cardiovascular functions in anesthetized rabbits. When MCR was injected to anesthetized rabbit at an intravenous dose of 100 mg/kg, a respiratory arrest followed by a cardiac arrest was observed. This effect was antagonized by either treatment with CaCl2 or artificial respiration. In slant test, MCR at a dose of 100 mg/kg (i.v.) in mice induced muscle relaxation. This effect was weakened by slowing the injection speed of the drug. Intravenous injection of MCR potentiated the lethality induced by either d-tubocurarine or succinylcholine. Intravenous injection of MCR influenced on neither pentobarbital sodium-, ethyl ether-, nor halothane-induced anesthesia in mice. From these results, intravenous infusion of MCR at a dose of 20 mg/kg/hour that is considered as 5 approximately 10 times of clinical dose (120 approximately 240 mg/day) did not influence on both respiration and cardiovascular functions.

Aminoglycosides↗
PubMed2002

Duration of anesthesia before muscle relaxant injection influences level of paralysis.

BACKGROUND: Dosage guidelines for muscle relaxants are based on dose-response studies, normally performed after several minutes of stable nitrous oxide (N O)-opioid anesthesia. However, relaxants are used immediately after induction of anesthesia. The study was designed to determine the influence of the duration of anesthesia and N O on the onset time at the adductor pollicis (AP) and the corrugator supercilii (CS) muscles of maximum neuromuscular blockade after mivacurium. METHODS: After institutional approval and informed consent, patients were randomly allocated into three groups. Anesthesia was induced with alfentanil and propofol. Group A (n = 10) received mivacurium (0.1 mg/kg) immediately after loss of consciousness. Groups B (n = 10) and C (n = 10) received mivacurium after 15 min of anesthesia with propofol alone (B) or propofol with N O (C). The evoked response to train-of-four stimulation was measured by acceleromyography at the AP and the CS. RESULTS: Maximum neuromuscular blockade (%T1, median [range]) was significantly less in group A than in groups B and C ( < 0.001) at both the AP (81 [47-90]; 90 [35-100]; 100 [93-100], respectively) and the CS (19 [5-63]; 68 [61-100]; 89 [72-100], respectively). Maximum neuromuscular blockade was less in group B than in group C ( < 0.001) at the AP. Onset time of maximum neuromuscular blockade was not different between groups but was shorter at the CS than at the AP. CONCLUSIONS: Duration of anesthesia and N O before mivacurium injection affect intensity of neuromuscular blockade but not onset time. Neuromuscular blockade obtained at the AP after several minutes of stable anesthesia with N O is greater than immediately after induction. This explains in part the discrepancy between the measured ED and the intubating dose.

Adult↗
PubMed1995

[Prolonged muscle paralysis after long-term infusion of muscle relaxants and large doses of steroids].

We have recently encountered three patients who developed prolonged muscle paralysis after long-term infusion of muscle relaxants and administration of large doses of steroids. Among many factors implicated in the cause of this paralysis, steroids and muscle relaxants were suggested to be most likely causative agents. In order to avoid such muscle paralysis, we must be careful to limit the dose of relaxants as small as possible. For this purpose, monitoring of neuromuscular blockade is indispensable.

Female↗
PubMed1999

Abnormal cortical processing of voluntary muscle relaxation in patients with focal hand dystonia studied by movement-related potentials.

In order to clarify the abnormality in cortical motor preparation for voluntary muscle relaxation of the hand in patients with focal hand dystonia, Bereitschaftspotentials (BPs) preceding voluntary muscle contraction and relaxation were recorded in eight patients (three with simple writer's cramp and five with dystonic writer's cramp), and were compared with those from 10 normal subjects. Voluntary muscle relaxation: after keeping the right wrist in an extended position for > 5 s, the subject let the hand drop by voluntarily terminating muscle contraction of the wrist extensor without any associated muscle contraction. Voluntary muscle contraction: the right wrist was flexed by voluntarily contracting the wrist flexor muscle. Scalp EEGs were recorded from 11 electrodes placed over the frontal, central and parietal areas. In the control group, the BP measured at the movement onset was maximal at the left central area (C1), and distributed predominantly over the left hemisphere equally in both the contraction and relaxation tasks. In the focal hand dystonia group, BP was maximal at C1 in the contraction task, whereas, in the relaxation task, it was maximal at the midline central area (Cz) and symmetrically distributed. At the left central area, the BP amplitude in the focal hand dystonia group was diminished significantly in the relaxation task compared with the contraction task (P < 0.05). The present results demonstrate for the first time that the cortical preparatory process for voluntary muscle relaxation, or motor inhibition, is abnormal in focal hand dystonia.

Adult↗