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PubMed1993

The effects of centrally acting muscle relaxants on the intrathecal noradrenaline-induced facilitation of the flexor reflex mediated by group II afferent fibers in rats.

The effects of centrally acting muscle relaxants on the flexor reflex mediated by group II afferent fibers (group II flexor reflex) in anesthetized intact rats and on the intrathecal noradrenaline-HCl-induced facilitation of the group II flexor reflex in anesthetized spinal rats were investigated. In anesthetized intact rats, mephenesin, tolperisone-HCl, chlorpromazine-HCl and baclofen inhibited the group II flexor reflex dose-dependently, whereas the inhibitory effect of tizanidine-HCl was bell-shaped. The effect of diazepam tended to be saturated. In anesthetized spinal rats, mephenesin, tolperisone-HCl, chlorpromazine-HCl, diazepam and baclofen also depressed the group II flexor reflex, but tizanidine-HCl slightly increased it. The intrathecal noradrenaline-HCl-induced facilitation of the group II flexor reflex was not affected by mephenesin or diazepam, but was inhibited by tizanidine-HCl, tolperisone-HCl, chlorpromazine-HCl and baclofen. These results suggest that compounds with centrally acting muscle relaxant activity depress the group II flexor reflex in different manners, and the inhibition of descending noradrenergic tonic facilitation within the spinal cord participates in the depressant action of the group II flexor reflex produced by tolperisone-HCl, tizanidine-HCl, chlorpromazine-HCl and baclofen.

Animals↗
PubMed1988

Lysolecithins as endothelium-dependent vascular smooth muscle relaxants that differ from endothelium-derived relaxing factor (nitric oxide)

The effects of lysolecithin (lysophosphatidylcholine) derived from egg yolk as well as of synthetic lysolecithins with different aliphatic chain lengths on tension development of rabbit aortic strips were investigated. Lysolecithins caused slowly progressing, dose-dependent relaxation that was inhibited by hemoglobin, methylene blue, and nordihydroguiaretic acid. Indomethacin caused no inhibition of relaxation. The degree of relaxation was endothelium-dependent and appeared to be related to the activation of guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2]. Superoxide dismutase failed to influence relaxation. Lysolecithins with the longest aliphatic chain were the most potent relaxants of aortic strips. The experiments suggest a role of lysolecithins through their weak detergent action on membrane dynamics of endothelial cells, resulting in the production of cyclic GMP and the relaxation of arterial smooth muscle. Lysolecithins differ in several respects from endothelium-derived relaxing factor. Endothelium-derived relaxing factor is an unstable humoral substance released from endothelium and is identical to nitric oxide, itself a labile substance causing vascular relaxation and cyclic GMP accumulation. Lysolecithins may represent a different type of endothelium-dependent muscle relaxant.

Acetylcholine↗
PubMed1989

[Predictive value of intradermal tests using muscle-relaxing drugs].

A retrospective postal inquiry was carried out to find out a possible relation between the results of intradermal tests carried out for a previous anaesthetic and the course of a second anaesthetic performed afterwards. This study included 350 patients who have had an intradermal test to vecuronium, alcuronium, suxamethonium, gallamine, pancuronium, thiopentone, fentanyl and droperidol between March 1984 and November 1986. Eighty-nine did not reply (25.4%), 183 (52.3%) did not undergo new general anaesthetic since the skin tests, whilst 78 (22.3%) did. The inquiry was then sent to the 73 anaesthetists corresponding to the last group of patients. The 51 complete answers included 62 anaesthetics. Twenty-four patients had negative intradermal tests before the new anaesthetic, the other 27 having had a test positive to at least one muscle relaxant. Of these latter, 16 were given a muscle relaxant during their general anaesthetic, selected among those resulting in a negative intradermal test. Thirteen had undergone skin testing because of an anaphylactic reaction during induction. No new anaphylactic reaction was observed. Three anaesthetists only were not aware of the results of the intradermal tests at the time of the new anaesthetic. These data tend to demonstrate that a muscle relaxant could be injected in a patient who has had a previous anaphylactic reaction with positive intradermal tests, provided that the drug chosen for the new anaesthetic does not give a positive intradermal reaction.

Adult↗
PubMed1969

An instrument for producing deep muscle relaxation by means of analog information feedback.

An instrument that assists subjects in attaining deep muscle relaxation by means of analog information feedback is described. Subjects hear a tone with a pitch proportional to the electromyographic activity in a given muscle group. Results showed that subjects receiving this type of analog feedback reached deeper levels of muscle relaxation than those receiving either no feedback or irrelevant feedback. The basic method employed-electronic detection, immediate information feedback, and systematic shaping of responses-would seem potentially applicable to a variety of physiological events, and might be useful both in behavior therapy and in certain psychosomatic disorders.

Journal Article↗
PubMed1987

Different spasmolytic effects of smooth muscle relaxants on the guinea-pig esophageal muscularis mucosae contracted by carbachol or high potassium in vitro.

The responsiveness of the guinea-pig esophageal muscularis mucosae to smooth muscle relaxants was examined in vitro during the contractile state induced by carbachol (3 microM) or high potassium (60 mM). In the presence of phentolamine (3 microM), all catecholamines tested (10 nM-30 microM) relaxed the carbachol-induced tone more effectively than the high potassium-induced tone, and the maximum relaxations reached about 90-95% for carbachol but only about 40% for high potassium. Verapamil produced a concentration-dependent relaxation of the muscularis mucosae precontracted with either spasmogen; the mean EC50 values (-log M) were 6.73 for high potassium and 4.65 for carbachol. Methylene blue (1-300 microM) relaxed the carbachol-contracted muscularis mucosae in a concentration-dependent manner but relaxed the high potassium-contracted one less potently. Forskolin (1-300 microM), papaverine (1-100 microM), aminophylline (10-300 microM), trifluoperazine (1-300 microM), 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (10-300 microM), quinacrine (1-300 microM) and dibutyryl cyclic AMP (100 microM-3 mM) produced relaxation almost equipotently in both contractile states whereas adenosine (10 microM-1 mM), sodium nitroprusside (10-300 microM) and dibutyryl cyclic GMP (100 microM-3 mM) were virtually ineffective. The present results indicate that a variety of smooth muscle relaxants have different spasmolytic effects on the guinea-pig isolated esophageal muscularis mucosae which was precontracted with carbachol or high potassium and that catecholamines and methylene blue may produce relaxation independent of the changes in intracellular cyclic nucleotides, calmodulin or phosphoinositides.

Animals↗
PubMed1991

Pre-clinical toxicity of IDPH-791: a new centrally acting muscle relaxant in rats.

IDPH-791, a novel centrally acting muscle relaxant, in doses up to 500 mg/kg (po) for 14 days did not result in any appreciable adverse effect on body weight gain, food or water consumption including biochemical and haematologica parameters in rats. Variations observed in the biochemistry and haematology were either comparable to controls or were within normal limits.

Animals↗
PubMed1994

[Differential effects of muscle relaxants on the evoked electromyogram of the thenar and hypothenar muscles].

This study compares the neuromuscular blocking effect of nondepolarizing relaxants on the thenar and hypothenar muscles in 14 anesthetized patients with nitrous oxide-halothane. Vecuronium (60 micrograms.kg-1 iv) or pancuronium (60 micrograms.kg-1 iv) was given and supramaximal stimulation was applied to ulnar nerve at the wrist. The evoked compound action potentials were measured over the thenar and hypothenar muscles of the right hand simultaneously. During vecuronium blockade, the ratios of single twitch depression (T1/Tc) and train of four (T1/T4) of the thenar muscle were comparable with that of the hypothenar muscle. There was significant higher T1/Tc and T1/T4 ratio for the hypothenar muscle than for the thenar muscle within 60 minutes from pancuronium administration. These data suggest that relative potency of muscle relaxant on these two muscles seems to be drug specific. This phenomenon brings certain practical difficulties on monitoring of neuromuscular function with evoked electromyogram during anesthesia.

Adolescent↗
PubMed1979

Centrally administered neurotensin: activity in the Julou-Courvoisier muscle relaxation test in mice.

Intracisternal (IC) neurotensin (NT) produces muscle relaxation in the Julou-Courvoisier traction test, a screening procedure utilized for assessing neuroleptic drug activity. A dose-response relationship was not observed. IC administration of thyrotropin-releasing hormone (TRH) totally abolished the effects of NT. Two other peptides, substance P and bradykinin, were inactive in the traction test. These data provide further evidence for CNS effects on NT and indicate that this peptide exerts neuroleptic-like activity in a screening test for antipsychotic agents.

Animals↗
PubMed1985

Leukocyte histamine release to suxamethonium in patients with adverse reactions to muscle relaxants.

In an earlier study we confirmed the usefulness of intradermal skin tests and histamine release in diagnosis of patients reactive to muscle relaxants, and we suggested an IgE-mediated reaction rather than an idiosyncratic mechanism. In a later study, we studied the relationship between (Formula: see text) that is one of the muscle relaxants producing the most frequent adverse reactions under anesthesia. Histamine release was measured in five patients with increasing concentrations of suxamethonium in the presence or absence of human serum albumin in Tris buffer. Suxamethonium by itself without any carrier in the buffer could, in vitro, act as a true allergen on target leukocytes in the sensitized patients' group. Acetylcholine (20 and 200 micrograms/ml) did not induce significant histamine release in five patients with positive histamine release in the presence of suxamethonium. Preincubation of leukocytes from 11 patients for 30 min with 20 and 200 micrograms of acetylcholine in Tris albumin CA++ Mg++ buffer decreased the histamine release induced by suxamethonium (10 micrograms/ml); mean maximal histamine release of 46% +/- 4.2 was reduced to 31.4 +/- 5.8 and 7% +/- 4 (p less than 0.001), respectively. However, in eight control subjects similar concentrations of acetylcholine did not change the maximal histamine release induced by anti-IgE (0.2 micrograms/ml). In the same way acetylcholine did not modify histamine release induced by Dermatophagoides pteronyssinus extract (1/10,000 w/v) in six patients allergic to this allergen. This study suggests that suxamethonium acts as a true allergen and that acetylcholine or one of its metabolites may act as a hapten inhibitor in the model of histamine release induced by suxamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

[Plethysmechanomyography (PMG). A simple method for monitoring muscle relaxation].

Ideal evaluation of neuromuscular blockade can be done by mechanical or electromyographical registration of muscle contractions evoked by ulnar nerve stimulation. Unfortunately, devices needed for such registration are expensive or complicated to set up, and thus are not often used for routine monitoring in anaesthesia. In this study, we describe a simple and low-priced method permitting intra- and postoperative monitoring of neuromuscular blocking agents. The accuracy of plethysmomechanomyography (PMG) was evaluated by comparing simultaneous electromyographic (EMG) and plethysmographic measurements. METHODS. For plethysmographic registration of muscle response to nerve stimulation a simple infusion system is twisted there to five times around one hand and connected to an anaesthetic monitor via a pressure transducer. The drip chamber is fixed about 20 cm above the hand (Fig. 1). Then, the infusion system is then filled up-with physiologic saline solution and the clamp is nearly closed. Electric stimulation can be carried out using any nerve stimulator. Using this method, PMG mainly records the contractions of abductor digiti minimi muscle, but also partly those of the interossei. Evoked muscle contractions cause stretching of the infusion system, which leads to pressure changes proportional to the strength of contraction. The muscle response to "train-of-four" (TOF) stimulation of the ulnar nerve was recorded simultaneously by EMG and PMG in 11 patients (ASA class I or II) undergoing neurosurgical procedures and therefore requiring muscle relaxation. After induction of anaesthesia by injection of etomidate and fentanyl, supramaximal stimulation and control values (T0) were defined. Anaesthesia was maintained by supplementation with nitrous oxide/oxygen (1:2) and muscle relaxation was carried out with vecuronium. We used the integrated nerve stimulator of a Datex Relaxograph NMT-100 EMG monitor and proceeded to stimulate the ulnar nerve at the forearm with supramaximal strength. The PMG was registered by a Siemens Siredoc 220 printer connected to a Siemens Sirecust 1281 anaesthetic monitor. First twitch ratio (T1/T0) and TOF ratio (T4/T1) were calculated from these recordings. The EMG recordings were made by a Datex Relaxograph NMT-100 monitor, which automatically computes T1/T0 and T4/T1. The comparison of EMG and PMG values was carried out by simple linear regression. Statistical evaluation was performed using analysis of variance. RESULTS. A plethysmographically registered graph of the TOF-evoked muscle response is illustrated in Fig. 2. Simultaneous EMG and PMG recordings of onset and recovery from a nondepolarizing blockade are shown in Fig. 3. A strong positive correlation (P < 0.001) of EMG and PMG was found with correlation coefficients of 0.98 for T1/T0 and of 0.97 for T4/T1. The mean difference between values of both methods was 5%, maximally 18% (T1/T0) and 20% (T4/T1). CONCLUSIONS. Mechanomyography and EMG are well established methods of neuromuscular monitoring. Our data demonstrate that PMG provides a reliable measurement of neuromuscular transmission that correlates well with EMG. Since only materials of daily use in anaesthesia are needed, no substantial costs will arise when the plethysmographic method of measurement is used for routine anesthetic monitoring.

Adult↗
PubMed1997

Long lasting smooth muscle relaxation by a novel PACAP analogue in guinea-pig and primate airways in vitro.

1. We compared the relaxant effect of pituitary adenylate cyclase activating peptide (PACAP) 1-27 with that of a newly developed PACAP 1-27 analogue, [Arg15,20,21Leu17]-PACAP-Gly-Lys-Arg-NH2, in the guinea-pig trachea and primate bronchi in vitro (n = 4-5). 2. In the guinea-pig trachea precontracted by a submaximally effective carbachol concentration (0.1 microM), cumulative administration of PACAP 1-27 and the beta 2-adrenoceptor agonist salbutamol (3 nM-3 microM) caused significant and concentration-dependent smooth muscle relaxation, with salbutamol being approximately one log-step more potent in this model. However, in primate bronchi precontracted by carbachol (0.1 microM), cumulative administration of PACAP 1-27 and salbutamol caused concentration-dependent smooth muscle relaxation with very similar potencies and maximum relaxant effects. 3. In the guinea-pig trachea, non-cumulative administration of the PACAP 1-27 analogue and the original PACAP 1-27 (0.3-3 microM) caused concentration-dependent relaxation with a very similar maximum relaxant effect and potency. However, the onset and offset of action was markedly slower for the PACAP 1-27 analogue than for the original PACAP 1-27 (< 90% versus < 10% of peak relaxation remaining 6 h after administration). Separate experiments confirmed that the PACAP 1-27 analogue also caused significant relaxation with slower onset and offset of action than did the original PACAP 1-27 in primate bronchi. 4. Peptidase inhibition by captopril (10 microM) and phosphoramidon (1 microM) significantly increased the maximum relaxant effect and duration of action of PACAP 1-27 but not of the PACAP 1-27 analogue, during the 3 h of observation in the guinea-pig trachea. 5. We conclude that [Arg15,20,21Leu17]-PACAP-Gly-Lys-Arg-NH2 produces significant, concentration-dependent and sustained airway smooth muscle relaxation in vitro. The sustained relaxant effect is due, at least in part, to the PACAP 1-27 analogue being less susceptible to cleavage by peptidases than the original peptide PACAP 1-27.

Albuterol↗
PubMed1997

Smooth muscle relaxing flavonoids and terpenoids from Conyza filaginoides.

Activity-guided fractionation of the smooth muscle relaxing, chloroform-methanol (1:1) extract of Conyza filaginoides (D.C.) Hieron (Asteraceae) led to the isolation of three flavonoids (quercetin 3-glucoside, rutin, and pinostrobin), one sterol (alpha-spinasterol), a sesquiterpenoid (beta-caryophyllene 4,5-alpha-oxide), and two triterpenoids (erythrodiol and 3-beta-tridecanoyloxy-28-hydroxyolean-12-ene). 3-beta-Tridecanoyloxy-28-hydroxy-olean-12-ene is a new naturally occurring terpenoid. All the isolated compounds induced a concentration-dependent inhibition of the spontaneous contractions of rat ileum. The spasmolytic activity exhibited by the extract and active principles tends to support the traditional use of C filaginoides as an antispasmodic agent.

Animals↗
PubMed1985

CGS 9896: agonist-antagonist benzodiazepine receptor activity revealed by anxiolytic, anticonvulsant and muscle relaxation assessment in rodents.

CGS 9896, a pyrazoloquinoline that potently binds to benzodiazepine receptors, has been reported to have anticonflict activity in conventional footshock paradigms and to antagonize pentylenetetrazol-induced seizures. In the present experiments, the pentylenetetrazol discriminative cue was blocked by CGS 9896 with a potency comparable to that of diazepam. CGS 9896 also selectively lengthened the latency to terminate self-initiated brain stimulation reward. These procedures extend the anxiolytic activity of CGS 9896 to models that do not rely upon footshock-induced conflict. CGS 9896 did not impair the traction reflex in mice, did not impair rotorod performance in rats, did not reduce unpunished operant responding and decreased motor activity only slightly, indicating no distinguishable sedation or muscle relaxation in rodent models. In fact, diazepam-induced rotorod impairment was blocked by CGS 9896. The anticonvulsant effects of CGS 9896, as indicated by audiogenic seizure and pentylenetetrazol-induced seizure studies, were substantial but were weaker than those of diazepam, possibly because of the muscle relaxant component of diazepam. Ethanol-induced motor impairment was potentiated more markedly by diazepam than by CGS 9896. Mixed agonist-antagonist properties of CGS 9896 therefore emerge when a comprehensive battery of behavioral assessments is utilized. CGS 9896 may have clinical anxiolytic activity without sedation or muscle relaxation.

Acoustic Stimulation↗
PubMed1988

Relaxation of isolated corpus cavernosum induced by smooth-muscle relaxant drugs. A comparative study.

Intracavernous injection of vasoactive substances are used in the treatment and investigation of impotence. We studied the effects induced by some pharmacological agents on strips of human erectile tissue. Specimens of corpus cavernosum were obtained from 16 men undergoing cystectomy or penectomy for bladder or penile malignancy. Strip preparations were mounted in thermostically controlled baths containing Krebs solution. Pharmacologic effects were monitored by means of an isotonic transducer. Papaverine was shown to be the substance able to cause the biggest relaxation effect. The authors compared the action of other drugs having a relaxant effect, studied the antagonist effects of epinephrine and dopamine on the pharmacologically relaxed preparations, and stressed that the relaxation of the erectile tissue has a determinant role in the appearance and maintenance of erection.

Adult↗
PubMed2000

[A senile case of acute necrotizing myopathy presenting prolonged severe muscle paralysis due to high dose glucocorticoid and muscle relaxant].

An 82-year old man was admitted with dyspnea, productive cough and wheezing. In addition to antibiotics (meropenem trihydrate 0.5 g/day), glucocorticoids (hydrocortisone 1.250 mg, methylpredonisolone 4.250 mg) were administered for the severe bronchospasms. Since his respiratory condition deteriorated, he underwent mechanical ventilation using a muscle relaxant (vecuronium bromide, total dose 776 mg) in combination with high dose glucocorticoid. As his pneumonia improved on the 10th hospital day, we started weaning him from the ventilator. However, we were unable to complete weaning from the ventilator because of prolonged quadriplegia and paralysis of the respiratory muscles. A few days later, myoglobinuria appeared. Electrophysiological examinations suggested the involvement of both neuromuscular junctions and muscles. Muscle biopsy showed rhabdomyolysis. Acute necrotizing myopathy was diagnosed due to high doses of glucocorticoid, muscle relaxant, or both. He required about 3 months to be weaned from the mechanical ventilation, and another 3 months to leave the hospital. Based on our experience, we should consider acute myopathy as an adverse effect of glucocorticoids, muscle relaxants or both in elderly patients who require mechanical ventilation.

Acute Disease↗
PubMed1998

Smooth muscle relaxation: effects on arterial compliance, distensibility, elastic modulus, and pulse wave velocity.

Compliance, distensibility, incremental elastic modulus (E(inc)), and pulse wave velocity are all terms used to describe the mechanical properties of arteries. Previous studies assessing the effects of smooth muscle relaxation on each of these parameters have produced conflicting results. Our laboratory has previously demonstrated that intrabrachial infusion of nitroglycerin in normal human subjects results in a large increase in brachial artery compliance without changing arterial wall stiffness as measured by E(inc). In the present study, the relationships among compliance, distensibility, E(inc), and pulse wave velocity under different levels of vascular tone are shown using data acquired by intravascular ultrasound as well as theoretical curves. We demonstrate that the effects of smooth muscle relaxation can be depicted as 2 separate steps: (1) a rightward shift to a new theoretical curve describing the relationship between 2 of the above elastic parameters that is solely due to changes in vessel geometry and (2) a shift along the new curve that is dependent on changes in wall stiffness.

Adult↗