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PubMed1981

[Haemodilution and duration of action of muscle relaxants (author's transl)].

As indicated by time-effect diagrams the duration of action of the ED90 of succinylcholine (0.3 mg/kg), pancuronium (0.033 mg/kg), and tubocurarine (0.21 mg/kg) was prolonged following preoperative normovolemic haemodilution. This influence is assumed to be due to a lower protein binding and cholinesterase activity, to an increase of cardiac output and muscle perfusion and to a higher occupancy of the receptor at the motor endplate by muscle relaxants.

Cardiac Output↗
PubMed1994

Induction of muscle-relaxing factor by staphylococcal alpha-toxin.

Brain tissue and serum from mice intracerebrally injected with 1 microgram of staphylococcal alpha-toxin contained elevated amounts of a naturally occurring brain tissue component(s) called muscle-relaxing factor (MRF). MRF induced reversible, generalized, flaccid paralysis of mice after intracerebral but not intraperitoneal or intravenous administration. MRF (i) was soluble in Hanks balanced salt solution and in acidified (pH 2) Hanks balanced salt solution, in which it partitions into ethyl acetate, acetone, and methanol; (ii) was separated from some pigments by thin-layer chromatography on silica gel plates; (iii) did not comigrate with prostaglandin and leukotriene standards during high-pressure liquid chromatography with a mu Bondapak fatty acid column; and (iv) did not contain amino acids, exhibit absorption maxima at a wavelength range of 210 to 600 nm, or fluoresce when exposed to UV light. MRF has been detected in rabbit brain that has been stored frozen at -70 degrees C and has been enhanced in vitro in slices of both mouse and rabbit brain following incubation of the brain slices with staphylococcal alpha-toxin. Studies to identify the chemical nature of MRF and the mechanism by which, in mice, it induces reversible, flaccid paralysis of voluntary muscle are continuing.

Animals↗
PubMed2003

[New findings on the synthesis of the centrally acting muscle relaxant chlormezanone and its resolution of a gram scale using a Chiralcel OD column].

2-(4-Chlorophenyl)-4-metathiazanone (2) is the intermediate product for the two step-synthesis of chlormezanone (1), a centrally acting muscle relaxant. The second step includes the oxidation of its sulfur atom. It has been found that the foregoing reaction of 4-chlorobenzaldehyde with methylamine forming the hemiaminale and the subsequent addition of beta-mercaptopropionic acid leads to a remarkable better yield (67% of th.) than the route via the hemimercaptale (42% of th.). 2 could be oxidized with sodium perborate superior to potassium permanganate. The racemic chlormezanone (1) is resolved quickly on a gram scale by preparative column chromatography on a Chiralcel OD column (tris(3,5-dimethyl-phenyl-carbamoyl)cellulose on silicagel). The resolution needed only 40 min, if flow rate, composition of the mobile phase and temperature as the most important factors are determined prior with an analytical column. Both dissociation constants could be determined for the first time with the aid of a log pKa-Titrator of the Sirius Co., which needs for the registration of the curves only 15-17 min in the pH range of 2-12. This speed outplayed the disturbing cleavage of the S-C bond of chlormezanone at strong acidic and alkaline pH values.

Chlormezanone↗
PubMed1988

Biochemical mechanisms underlying vascular smooth muscle relaxation: the guanylate cyclase-cyclic GMP system.

Several classes of vasodilators have been demonstrated to elicit their affects by activating guanylate cyclase and elevating intracellular concentrations of cyclic GMP. The nitrovasodilators, such as nitroglycerin, generate nitric oxide, which directly activates the soluble isoenzyme of guanylate cyclase resulting in increased intracellular concentrations of cyclic GMP. A second class of agents, the endothelium-dependent vasodilators, such as acetylcholine, requires an intact endothelium to elicit vascular smooth muscle relaxation, in contrast to the nitrovasodilators. These agents stimulate the release of an endothelium-derived relaxing factor (EDRF), which also activates the soluble form of guanylate cyclase, triggering the production of cyclic GMP. The third class of agents includes atrial natriuretic peptides (ANPs). These low-molecular-weight, heat-stable peptides bind to specific receptors on vascular smooth muscle. These receptors appear unique in that they have a dual function possessing both ANP binding and particulate guanylate cyclase activities. Binding to and activation of particulate guanylate cyclase, in the absence of endothelium, results in the elevation of intracellular concentrations of cyclic GMP and relaxation.

Animals↗
PubMed1982

Org-NC45: a new steroidal non-depolarizing muscle relaxant.

Although pancuronium has fewest side effects compared to other currently used non-depolarizing muscle relaxants, it is still not the ideal relaxant. Its structural analogues have been studied to derive such an ideal relaxant. Org-NC45 meets the requirements for such a relaxant best and is therefore extensively studied. It is more potent than pancuronium, has a shorter onset and duration of action and is free from cardiovascular side effects. Histamine release could not be demonstrated. It can be easily reversed by neostigmine, pyridostigmine or 4-aminopyridine. Interaction with antibiotics and anaesthetic drugs is not different from that of pancuronium.

Humans↗
PubMed1994

Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome.

AIM: To assess the efficacy of smooth muscle relaxants in the treatment of patients with irritable bowel syndrome, a meta-analysis of 26 selected double-blind randomized trials vs. placebo was performed. METHODS: Five end-points were assessed: global assessment, abdominal pain, constipation, abdominal distension and the absence of adverse reactions. Analyses were performed according to the intention-to-treat method. For each end-point, the drug efficacy was assessed by the Der Simonian and Peto methods. When a significant difference was observed, sensitivity analyses were performed by successive stratifications according to the type of drug, the treatment duration, the prevalence of constipated patients, the trial design and the methodological quality. RESULTS: All myorelaxants analysed were significantly better than placebo for the improvement of global assessment (62% improvement rate vs. 35% on placebo, that is 27% improvement rate, P < 0.01) and for pain improvement (64% improvement rate vs. 45% on placebo, that is 19% improvement rate, P < 0.01). No significant differences were observed for constipation and abdominal distension. The percentage of patients with adverse reactions was significantly higher in patients receiving myorelaxants than placebo (6% mean difference, P < 0.01). CONCLUSION: According to this overview five drugs have proved their clinical efficacy in patients with irritable bowel syndrome, without significant adverse reactions: cimetropium bromide, pinaverium bromide, trimebutine, octilium bromide and mebeverine.

Colonic Diseases, Functional↗
PubMed1982

Chlordiazepoxide-induced ataxia, muscle relaxation and sedation in the rat: effects of muscimol, picrotoxin and naloxone.

Chlordiazepoxide-induced ataxia was potentiated by muscimol (0.5 mg/kg) and antagonised by picrotoxin (2 and 4 mg/kg) and by naloxone (2 and 4 mg/kg). The muscle-relaxant effects of chlordiazepoxide were not significantly altered by any of these three drugs and nor was the chlordiazepoxide-induced decrease in exploratory head-dipping. However, the sedative effects of chlordiazepoxide, measured by a reduction in spontaneous motor activity, were antagonised by picrotoxin.

Animals↗
PubMed1988

[Effect of muscle relaxants on intraocular pressure].

Since general anesthesia is being used increasingly in ophthalmic surgery, the effects of anesthetic drugs on intraocular pressure (IOP) have to be considered. Competitive neuromuscular blocking drugs either do not affect IOP or produce a slight decrease. Depolarizing muscle relaxants increase IOP. This effect, which is pronounced with succinylcholine, cannot be reliably prevented by any concomitant medication. The new competitive relaxants atracurium and vecuronium provide stable conditions with respect to IOP and systemic circulation, combined with fast onset and intermediate duration of action.

Anesthetics↗
PubMed1994

In-vitro smooth muscle relaxant activity of a series of vecuronium analogues in the rat aorta.

The ability of a series of 17-ester analogues of vecuronium to elicit a direct relaxant effect on vascular smooth muscle has been studied using rat isolated aortic rings contracted with 40 mM KCl. The IC50 for inhibition of KCl-induced contractions increased with increasing size of the 17-ester substituent, such that vecuronium (17 beta-acetate) was the least potent with an IC50 of around 50 microM and Org-9827 (17 alpha-pivalate) was the most potent with an IC50 of around 5 microM. In addition, for the weaker-acting compounds, the 17 alpha-esters were more potent than their corresponding 17 beta-esters, although this difference was lost as the size of the 17-ester substituent increased. From the results obtained here, it is concluded that the hypotensive activity of some of the newer neuromuscular blocking steroids seen in cats, pigs and dogs in-vivo is probably, at least in part, a consequence of a direct relaxant effect of the compound on vascular smooth muscle through inhibition of voltage-activated, L-type, calcium channels. This may have both advantageous and disadvantageous clinical consequences when using large doses of one of the newer vecuronium analogues with a low relative neuromuscular-blocking potency.

Animals↗
PubMed1988

Intraosseous infusion of muscle relaxants.

This case report presents the resuscitation of a 6 1/2-month-old child with elevated intracranial pressure, seizure activity, and a presumptive diagnosis of shaken child syndrome. It is unique in the usage of an intraosseous infusion line for the administration of muscle relaxants and anesthetic agents to aid in an atraumatic intubation in this head-injured child. This is an original report of the usage of the intraosseous line for the administration of succinylcholine chloride, atracurium besylate, and thiopental sodium.

Accidental Falls↗
PubMed2002

A survey of practice of tracheal intubation without muscle relaxant in paediatric patients.

BACKGROUND: Because of the renewed interest in intubation in children without relaxants, over a period of 1 month, the anaesthesiologists of five paediatric universitary teaching hospitals were asked to complete a questionnaire each time they performed a tracheal intubation without muscle relaxant. METHODS: Intubating conditions were assessed with five items. Each item was graded on a four-point scale. Intubating conditions were judged acceptable when all items scored 2 or less. Episodes of oxygen desaturation and failed intubations were noted. Data are expressed as mean +/- SD (extremes). RESULTS: Five hundred and two questionnaires were completed during the study period. Children were aged 61 +/- 50 (1-180) months old. Induction of anaesthesia was performed with sevoflurane for 62.6% of the children (endtidal concentration 5.9 +/- 1.5%) and propofol for 28.9% (dose 5.8 +/- 4.2 mg x kg(-1). Opioids were associated with these hypnotics in 53.2% of the children. Tracheal intubation was successful in 87.1% of the children. Sevoflurane produced better intubating conditions than propofol. Sevoflurane requirements for tracheal intubation may be higher in infants aged less than 6 months old than in older children. A severe decrease in SpO2 (< or = 90%) was observed in 15.9% of the infants aged less than 1 year old and in 1.7% of the children, respectively (P < 0.0001). CONCLUSIONS: Sevoflurane is the most commonly used agent for tracheal intubation without relaxants with higher doses being required in infants aged less than 6 months. Propofol, even with opioids, was not so successful.

Adolescent↗