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PubMed1988

Inhibition of vascular smooth muscle relaxation by LY83583.

The ability of LY83583 to antagonize vascular smooth muscle relaxation elicited by a number of vasodilators was examined in rings of rat aorta. LY83583 (0.3-10 microM) inhibited relaxant responses to acetylcholine, calimycin (A23187), adenosine triphosphate (ATP) and sodium nitroprusside, whereas responses to atriopeptin III an activator of particulate guanylate cyclase, and papaverine were unaffected. For acetylcholine and calimycin the major effect of LY83583 (0.3-10 microM) was to reduce the maximal response without appreciably altering the EC50 values whereas for ATP the EC50 values were markedly increased by low concentrations of LY83583 (0.3-1 microM) with depression of maximal responses occurring at higher concentrations (10 microM) of the antagonist. In contrast LY83583 produced nonparallel rightward shifts of the curve for sodium nitroprusside without altering the maximal response. In addition, LY83583 (10 microM) reduced basal levels of cyclic GMP and prevented acetylcholine and sodium nitroprusside-induced elevations of cyclic GMP, in parallel with reductions in the relaxant responses. In the presence of LY83583 (10 microM) higher concentrations of sodium nitroprusside restored both the relaxant response and the elevation of cyclic GMP. The results of this study show that LY83583 antagonises only those vasodilators which are thought to act via stimulation of soluble guanylate cyclase. The nonsurmountable inhibition of relaxation to acetylcholine, calimycin and ATP probably reflects a limited maximal capacity of the endothelium to release EDRF in response to these agents.

Acetylcholine↗
PubMed1994

A literature review of the newest muscle relaxant: ORG 9426.

This article reviews the literature on the newest muscle relaxant, ORG 9426. It has completed clinical trials in the United States and is awaiting final approval from the Food and Drug Administration. Research is presented in regards to the potency, chemical structure, mechanism of action, neuromuscular effects, cardiovascular effects, and possible drug interactions of ORG 9426. Its effect on renal and liver failure patients and on the pediatric and elderly population is also documented. The pharmacodynamics and pharmacokinetics are compared with other neuromuscular blocking agents based on current reports. ORG 9426 is a promising, effective, and rapidly acting muscle relaxant that offers several advantages over other neuromuscular blocking agents presently available.

Adult↗
PubMed1990

Muscle relaxation rates in individuals susceptible to malignant hyperthermia.

Muscle relaxation rate following a tetanic stimulus of adductor pollicis muscle was measured prospectively in 26 patients potentially susceptible to malignant hyperthermia (MH) the day before a muscle biopsy was obtained for MH in vitro screening. Eleven subjects were found to be MH susceptible (MHS) and 15 subjects MH-negative (MHN). In all patients, relaxation rate was recorded at three different temperatures of the skin overlying adductor pollicis (30, 34 and 38 degrees C) achieved by a small surface heating unit placed over the thenar eminence. The MHS group exhibited slightly higher relaxation rate at 34 and 38 degrees C compared with the MHN group and this difference was accentuated with increasing temperature, but was not statistically different. The results of the present study suggest that relaxation rates are normal in MHS individuals under physiological conditions and cannot be used diagnostically for MH screening.

Adult↗
PubMed1999

Visual estimation of onset time at the orbicularis oculi after five muscle relaxants: application to clinical monitoring of tracheal intubation.

UNLABELLED: The onset time of neuromuscular blockade at the adductor pollicis (AP) is different among neuromuscular blocking drugs, but these discrepancies had never been studied at the orbicularis oculi (OO). The purpose of this study was to verify if the differences in onset time observed at the AP still existed at the OO and to score the intubating conditions using monitoring at the OO after five muscle relaxants. The study included 172 adults aged 18-75 yr. Anesthesia was induced with fentanyl and propofol. Atracurium (0.5 mg/kg), mivacurium (0.20 mg/kg), rocuronium (0.6 mg/kg), succinylcholine (1.0 mg/kg), or vecuronium (0.08 mg/kg) was injected by random allocation. Time to complete disappearance of the response at the OO was assessed visually after train-of-four stimulation of the facial nerve. Laryngoscopy was then performed, and intubating conditions were determined on a scale of 1-4. Results were based on 150 patients. Onset time at the OO was (mean +/- SD): succinylcholine (57 +/- 17 s) < mivacurium (99 +/-19 s) = rocuronium (99 +/- 47 s) < atracurium (129 +/-33 s) = vecuronium (135 +/- 38 s) (P < 0.05). Overall intubating conditions were excellent (84%), good (14%), poor (1.3%), impossible (0.7%), and were similar among the five groups. We conclude that differences in onset time of muscle relaxants observed at the AP were also found at the OO. Visual estimation of the response at the OO correctly predicted good-to-excellent intubating conditions in more than 90% of cases for all the currently available muscle relaxants. IMPLICATIONS: Onset time of neuromuscular blockade, as estimated visually at the orbicularis oculi, depends on the muscle relaxants given. Regardless of the relaxant used, intubating conditions at loss of orbicularis oculi are acceptable.

Adolescent↗
PubMed2002

Activation of the midbrain periaqueductal gray induces airway smooth muscle relaxation.

In this study, we examined effects of chemical stimulation of the ventrolateral region of the midbrain periaqueductal gray (vl PAG) on airway smooth muscle tone. We observed that in anesthetized, paralyzed, and artificially ventilated ferrets, vl PAG stimulation elicited airway smooth muscle relaxation. To clarify the mechanisms underlying this observation, we examined the GABA-GABA(A) receptor signaling pathway by 1) examining the expression of GABA(A) receptors on airway-related vagal preganglionic neurons (AVPNs) located in the rostral nucleus ambiguus region (rNA), by use of receptor immunochemistry and confocal microscopy; 2) measuring GABA release within the rNA by using microdialysis; and 3) performing physiological experiments to determine the effects of selective blockade of GABA(A) receptors expressed by AVPNs in the rNA region on vl PAG-induced airway relaxation, thereby defining the role of the GABA(A) receptor subtype in this process. We observed that AVPNs located in the rNA region do express the GABA(A) receptor beta-subtype. In addition, we demonstrated that activation of vl PAG induced GABA release within the rNA region, and this release was associated with airway smooth muscle relaxation. Blockade of the GABA(A) receptor subtype expressed by AVPNs in the rNA by bicuculline diminished the inhibitory effects of vl PAG stimulation on airway smooth muscle tone. These data indicate, for the first time, that activation of vl PAG dilates the airways by a release of GABA and activation of GABA(A) receptors expressed by AVPNs.

Animals↗
PubMed1991

Comparative effects on psychomotor performance of the muscle relaxant afloqualone, alone and with ethanol.

The purpose of this study was to investigate the interaction between 40 mg afloqualone, a new centrally acting muscle relaxant and 0.5 g/kg ethanol using a double-blind three-way cross-over trial in which subjects were each given afloqualone with ethanol, ethanol alone and afloqualone alone. We first compared the effects of 40 mg oral afloqualone and 15 mg diazepam (considered as a reference drug) on the psychomotor and cognitive performance and muscular relaxation of 12 healthy male volunteers. Performance was assessed by six objective tests and eight visual analogue self-rating scales. All the above treatments were separated by a 2-week interval. Volunteers performed the objective tests 1 h after drug ingestion, and the self-rating scale evaluations before drug intake and 1, 3.5, 6 and 8 h thereafter. Afloqualone impaired psychomotor performance less than diazepam as shown by the number of correct answers in the digit symbol cancellation test and the time needed to complete this test. However, the measurement of the frontalis muscle action potential showed that the muscle relaxant activity of 40 mg afloqualone was equivalent to that of 15 mg diazepam. Furthermore, afloqualone given at an effective relaxant dose did not enhance the effects of a single dose of ethanol which predominated on either psychomotor performance or subjective feelings.

Administration, Oral↗
PubMed1998

Requirements for muscle relaxation in Friedreich's ataxia.

Friedreich's ataxia is an inherited disorder of the nervous system, requiring special care during anaesthesia, because of increased sensitivity to muscle relaxants. We report a case of Friedreich's ataxia in a 31-year-old woman, anaesthetised on two occasions, for tendinoplasty and pes cavus repair. Atracurium was used for neuromuscular blockade and monitored by a train-of-four twitch technique. The patient's response was normal. She returned to adequate spontaneous breathing within 20 min of the last dose of the muscle relaxant without need for anticholinesterase administration. When neuromuscular function is monitored, normal doses of muscle relaxant can safely be used in these patients.

Adult↗
PubMed1985

[Anaphylaxis to muscle relaxants. Predictive value of intradermal tests and study of crossed anaphylaxis].

37 patients were studied, all of whom presented with anaphylaxis to a muscle relaxant. The diagnosis was made after simultaneous intradermal testing (IDT), human basophil degranulation tests (HBDT) and Prausnitz-Küstner tests (PK) of passive cutaneous anaphylaxis. Three tests were positive in 6 patients, both IDT and PK in 9, and both IDT and HBDT in 8. In 14 patients, the IDT, repeated twice, were positive both times. A search for crossed anaphylaxis to the other muscle relaxants was carried out in all the patients during a second series of tests, a few months to years after the first one. The drugs tested, at dilutions of the pharmaceutical preparation of 10(-3) or more, were: suxamethonium, gallamine, alcuronium, pancuronium, vecuronium, d-tubocurarine. The reliability of IDT in the diagnosis of anaphylaxis is discussed in terms of the small reactive concentration, the producibility of the tests, the one HBDT that did become positive later, and in one case the occurrence of shock by crossed anaphylaxis. Skin reactivity seemed to remain constant with time, so allowing the use of IDT as a diagnostic tool, in cases of old anaphylactoid shocks, occurring during general anaesthetics. The frequency of crossed anaphylaxis was assessed to be about 84%. The sensitivity to one or other drugs varied with each patient. Pancuronium and vecuronium appeared to be the least likely drugs to cause crossed anaphylaxis. The predictive use of these tests is discussed. It is also suggested that muscle relaxants with only one quaternary ammonium group should be used, this chemical characteristic probably reducing the risks of sensitization.

Adolescent↗
PubMed1987

Multiform combination effects of smooth muscle relaxants with antitumor agents in rat ascites hepatoma AH66 cells.

At non-cytotoxic concentrations, actions of smooth muscle relaxants except for the action of isoproterenol (IPN) on the effect of vinblastine (VBL) and mitomycin C (MMC) in rat ascites hepatoma AH66 cells resistant to these antitumor agents clearly separated into two groups. IPN hardly influenced the effects of both VBL and MMC. Although verapamil, a calcium-antagonist, and W-7, a calmodulin inhibitor, enhanced the growth-inhibitory effect and uptake of VBL by inhibiting the VBL efflux, these drugs did not influence the effect and uptake of MMC. In contrast, forskolin, an adenylate cyclase activator, db-cAMP, a cAMP analog, and theophylline, a cyclic nucleotide phosphodiesterase inhibitor, potentiated the effect of MMC, but did not influence the effect of VBL. The combination effect of forskolin and db-cAMP might be elucidated from the increase of inward transport of MMC through the action of the intracellular cAMP elevated by these drugs. Theophylline, however, only slightly increased both intracellular cAMP level and MMC uptake into the cells, similar to the action of IPN. We thought that the combination effect of theophylline was effected through its other activity of repair inhibition against AH66 cells, which are resistant to MMC due to their high capacity to repair impaired DNA. Thus, the smooth muscle relaxants used in this study enhanced the growth-inhibitory effect of a distinct antitumor agent through their individual activity against tumor cells.

Animals↗
PubMed1983

Chemostructural requirement for centrally acting muscle relaxant effect of magnolol and honokiol, neolignane derivatives.

Effects of some diphenyl and monophenyl compounds on grip strength in mice and spinal reflexes in young chicks were investigated in order to study structure-activity relationships between muscle relaxant activity and neolignane compounds, magnolol and honokiol extracted from Magnolia officinalis THUNB. Diphenyl produced a long-lasting suppression in the spinal reflex and relatively weak inhibition in the grip strength. An introduction of a hydroxyl into 2-position of diphenyl, o-phenylphenol, increased the muscle relaxant activity and accelerated the onset, although the duration was still long. In the spinal reflex preparation the duration of action became short. The introduction of two hydroxyls into 2- and 2'-position of diphenyl, 2,2'-dihydroxydiphenyl, further strengthened the activity and shortened the duration of the inhibitory effect on the grip strength and the spinal reflex. When two allyls are introduced into 5,5'-position of 2,2'-dihydroxydiphenyl, it corresponds to magnolol. Magnolol, 5,5'-diallyl-2,2'-dihydroxydiphenyl, produced potent inhibitory effects of gradual onset and of long duration on the two test preparations. Position of allyls and hydroxyls in honokiol, 5,3'-diallyl-2,4'-dihydroxydiphenyl, is different from magnolol, although the pharmacological characteristics are quite similar to magnolol. These results suggest that a hydroxyl accelerates the onset and shortens the muscle relaxant activity of diphenyl and an allyl influences the activity in the opposite direction. Both radicals appear to intensify the activity.

Animals↗
PubMed1985

[Nifedipine and vecuronium bromide. How does a patient treated with calcium antagonists react to nondepolarizing muscle relaxants? Brief scientific communication].

The muscle-relaxation reactions of Ca-antagonist (nifedipine) pretreated patients and a control group (5 in each group) were observed after administration of vecuronium bromide using the "priming principle." Twitch depression induced by the "priming dose" of vecuronium bromide (20 micrograms/kg body weight and T4/T1 ratio in the Ca-antagonist-treated patients (35 +/- 13% and 0.42 +/- 0.14%, respectively), was significantly different (P less than 0.01) when compared with the control group (1.2 +/- 2.7% and 0.75 +/- 0.15%). Similarly, the onset time to maximum blockade after the intubating dose of vecuronium bromide (60 micrograms/kg body wt.) was significantly shorter in the nifedipine group (40 +/- 21 s) when compared with the controls (100 +/- 17 s). The duration of the effect observed clinically (until 25% recovery) in the nifedipine group 32.9 +/- 7.3 min versus 25 +/- 8.15 min was enhanced; however, the difference between the treated group and the control group was not significant.

Aged↗
PubMed2003

[A study of mechanical ventilation pattern in different recovery stages of muscle relaxant after general anesthesia].

OBJECTIVE: To observe the effects of intermittent positive pressure ventilation (IPPV), synchronized intermittent mandatory ventilation (SIMV), and biphasic intermittent positive airway pressure (BiPAP) on the recovery time of automatic breathing in patients in different stages of recovery of general anesthesia with muscle relaxant. METHODS: Thirty patients were randomly divided into three groups. The initial ventilation pattern was IPPV for all patients. After the last dose of muscle relaxant, the pattern of ventilation of group II and group III was adjusted to SIMV and BiPAP, respectively. The airway peak pressure(Ppeak), minute ventilation(MV), expiration carbon dioxide(P(Et)CO(2)), blood gases, and the interval between the last dose of muscle relaxant and automatic breathing(LR-S) was observed. RESULTS: (1) When T(1) appeared, Ppeak of the BiPAP group was lower than that of the IPPV group and SIMV (all P<0.01). When T(R)=0.75, Ppeak of IPPV group was lower compared with the SIMV and BiPAP groups (all P<0.01). (2) When T(1) re-appeared, the MV of BiPAP was higher than that of the IPPV group (P<0.05), but was not different from that of the SIMV group (P>0.05). When T(4) appeared, T(R)=0.25, T(R)=0.75, MV of SIMV group and BiPAP group was higher than that of IPPV group (all P<0.01). (3) When T(R)=0.25, T(R)=0.75, the P(Et)CO(2) of the SIMV group and BiPAP group was lower than that of IPPV group (all P<0.05). (4) Partial pressure of carbon dioxide in artery (PaCO(2)) of the SIMV and BiPAP group was lower than that of the IPPV group (all P<0.05). (5) The LR-S before extubation was shorter in SIMV and BiPAP group than that in IPPV group (P<0.05). CONCLUSION: SIMV and BiPAP have the advantages as follows: no confrontation between mechanical ventilation and autonomous breathing, quick recovery of autonomous breathing, little change in airway pressure, high MV and low P(Et)CO(2). So SIMV and BiPAP are more suitable for recovery from anesthesia. In addition, BiPAP can lower the airway's peak pressure and decrease the probability of barotrauma therefore it is more suitable for those patients with high airway pressure.

Adult↗
PubMed1992

[Neuromyopathy induced by halothane anesthesia and muscle relaxants for status asthmaticus--report of 2 patients].

Two patients with status asthmaticus (a 30-year-old female and a 48-year-old male) who developed flaccid quadriplegia and sensory impairment of glove and stocking type after treatment with halothane, muscle relaxants (pancuronium and vecuronium) and steroid are described. They noted motor and sensory impairment immediately after recovery from control ventilation for treatment of status asthmaticus. Histochemical examinations of biopsied muscle demonstrated the necrosis and regeneration of muscle fibers and small diameters in type I fibers. These results suggested that the involvement of muscle (myopathy) was a consequence of the harmful action of halothane and muscle relaxants together with steroids on muscle fibers with subclinical fragility. The sensory impairment (neuropathy) was considered to have been produced mainly by the halothane together with muscle relaxants and aminoglycosides.

Adult↗
PubMed1983

New muscle relaxants.

There are many new neuromuscular blocking drugs now going through the clinical trials required before new drugs can be used clinically on a routine basis. It is safe to say that within the next five years the muscle relaxants now in common use will be replaced by new and more "ideal" muscle relaxants. This review has attempted to define for the practicing anesthesiologist the goals of muscle relaxant research and the drugs that have been developed from that research. It is hoped that some familiarity with these drugs before they become widely available may hasten their extensive use by practitioner in the interest of better anesthetic patient care.

Androstane-3,17-diol↗
PubMed1983

Reversal of the muscle relaxant effect of diazepam but not of progabide by a specific benzodiazepine antagonist: Ro 15-1788.

The muscle relaxant effects of diazepam and progabide were studied in mutant Han-Wistar rats which exhibit spontaneous tonic activity in the electromyogram of the gastrocnemius-soleus muscle. Treatment with diazepam or progabide produced a dose-related reduction of the spontaneous activity measured in the electromyogram. The depressant effect of diazepam, but not that of progabide was antagonized by the specific benzodiazepine antagonist Ro 15-1788. From these data it is apparent that the muscle relaxant effect of progabide is not mediated through an alteration of benzodiazepine receptors.

Animals↗
PubMed1994

Effects of cyclic GMP on smooth muscle relaxation.

Cyclic GMP levels within smooth muscle are affected then by a number of different pathways. Physiologically NO and ANF are probably the two most important regulators for smooth muscle function, but a variety of other mediators and pharmacological agents may also influence this system. Because of the important role that cyclic GMP plays in the control of smooth muscle tone, which clearly includes vascular smooth muscle, it is now and will continue to be in the future an important physiological and biochemical target for research and a pharmacological target for therapeutic agents.

Animals↗
PubMedDate not supplied

Prevention by monovalent haptens of IgE-dependent leucocyte histamine release to muscle relaxants.

The cross-reactivity between muscle relaxants (MRs) is a risk for inducing anaphylaxis in sensitized patients. The preventive use of monovalent haptens (MHs) was studied in 21 cases. Inhibition of the skin reactivity by mixing MRs and MHs was observed, as was the inhibition of leucocyte histamine release to MRs, up to 3 h after infusion of MHs. These results argue for the use of such a protocol, if surgery requires the use of a MR in patients at risk for anaphylaxis.

Adult↗
PubMedDate not supplied

New developments in nondepolarizing muscle relaxants.

Anesthesiologists perceive that the ideal muscle relaxant is not yet available, particularly the nondepolarizing one with a rapid onset and a short duration of action. There is also a need for relaxants with different durations of action but which would be free from side effects. During the process of this development several new compounds have been tested and four have reached an advanced state of study; three of these, doxacurium, pipecuronium, and mivacurium are already licensed and rocuronium is likely to be licensed in the near future. Doxacurium and pipecuronium are slow onset and long duration of action compounds but singularly free from cardiovascular side effects. Mivacurium has an onset comparable to that of atracurium and vecuronium but with a duration of action which is intermediate in duration between these drugs and succinylcholine. Rocuronium is a drug with a fast onset of action capable of being used in place of succinylcholine but with a duration of action which is similar to that of vecuronium.

Anesthesiology↗