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PubMed1990

Hepatic transport mechanisms for bivalent organic cations. Subcellular distribution and hepato-biliary concentration gradients of some steroidal muscle relaxants.

In order to characterize the hepato-biliary transport of bivalent cations in more detail, the subcellular distribution of three steroidal muscle relaxants, that differ physicochemically and kinetically, was studied by differential centrifugation of liver homogenates. Binding of the muscle relaxants to macromolecular compounds was measured in Krebs-albumin solution, in cytosolic fraction of liver homogenate and in bile, to estimate the unbound concentrations in the particular fluids. Cytosol/plasma concentration ratios increased in the order pancuronium less than Org 6368 less than vecuronium, but for all of the compounds did not exceed the value that would be attained by passive equilibration according to the membrane potential. The subcellular distribution patterns of the three substances indicated that the mitochondrial fraction is a major storage compartment in the liver. Yet Org 6368 was bound to the particulate fraction of liver homogenate to a larger extent than pancuronium and vecuronium. The high bile/cytosol concentration ratios indicate that for all of these cations an active transport system is involved in the biliary excretion process. For Org 6368 and vecuronium the bile/cytosol concentration ratios are in the same range (about 30) and substantially higher than for pancuronium (about 6). This suggests that for Org 6368 and vecuronium the transport across the canalicular membrane is more efficient than for pancuronium. The combined data indicate that the extensive binding of Org 6368 to particles within the cell is a major factor in the relative efficient hepatic uptake and the modest biliary excretion of this agent. The limited hepato-biliary transport of pancuronium appears to be due to a relatively small net transport, both at the sinusoidal land at the canalicular membrane.

Animals↗
PubMed1987

Smooth muscle relaxing, acute and long-term blood pressure lowering effects of atriopeptins. Structure-activity relationship.

The relationship between the arterial relaxing, acute and long-term blood pressure lowering effects of atriopeptins were analyzed. We therefore evaluated effects of atriopeptin (103-126), i.e., atriopeptin III, and compared them to those of selected analogs. Atriopeptin (103-126) relaxed isolated aortas (1-30 nM) and lowered systolic blood pressure in conscious spontaneously hypertensive rats when high doses (4-400 nmol/kg i.v.) were administered acutely or low doses (0.4-4.0 nmol/kg/hr i.v.) were administered chronically. The relaxing effect was not affected by amino-terminal extension with up to four amino acids and by carboxy-terminal deletion of one amino acid. Further deletions lowered the relaxing potency. The observed maximal amplitude of the acute blood pressure lowering was reduced drastically by carboxy-terminal deletion of even one amino acid. This was prevented by substitution of the carboxy-terminal acid by an amide. Although not affecting the amplitude, amino-terminal extension with Arg or Arg-Arg prolonged markedly the duration of action of the acute effect. Chronic administration of atriopeptin (103-126), (103-125) and (103-123) affected blood pressure similarly. These findings illustrate different structure-activity relationships for the smooth muscle relaxing, acute and long-term antihypertensive activities of atriopeptins. From this it is suggested that the carboxy-terminal amino acids modulate differently the biological activities of atriopeptins, that amino-terminal amino acids modulate the duration of action of the acute in vivo effects and that the long-term antihypertensive effects of atriopeptins are not related directly to their arterial smooth muscle relaxing and acute blood pressure lowering effects.

Amino Acid Sequence↗
PubMedDate not supplied

Attenuation of cyclic nucleotide-mediated smooth muscle relaxation in blacks as a cause of racial differences in vasodilator function.

BACKGROUND: Vasodilator reactivity is attenuated in normotensive blacks, and this may contribute to their enhanced susceptibility to hypertension and its complications. However, the mechanisms responsible for this phenomenon are unknown. We therefore studied nitric oxide (NO)-dependent and -independent vasorelaxation in healthy blacks and whites to investigate the nature of racial differences in vasodilator function. METHODS AND RESULTS: Forearm flow responses to intra-arterial infusion of increasing doses of acetylcholine (a vasodilator that stimulates endothelial release of NO), sodium nitroprusside (an exogenous NO donor), and isoproterenol (a beta-adrenergic agonist whose vasodilator effect stems from the combination of direct smooth muscle stimulation and endothelial NO release) were studied in 18 normotensive whites and 18 blacks by use of strain-gauge plethysmography. A blunted vasodilator response to acetylcholine (7.2+/-1.1 versus 14.4+/-1.8 mL. min-1. dL-1; P<0.001) and sodium nitroprusside (8.2+/-1.1 versus 12.1+/-1.3 mL. min-1. dL-1; P<0.001) was observed in blacks compared with whites, suggesting decreased cGMP-mediated smooth muscle relaxation. The vasodilator effect of isoproterenol was lower in blacks than in whites both before (10.9+/-1.7 versus 14.9+/-1.5 mL. min-1. dL-1; P=0.006) and after NG-monomethyl-L-arginine (6.1+/-1.2 versus 10. 1+/-0.8 mL. min-1. dL-1; P<0.001), implying that cAMP-dependent vasodilator response to isoproterenol is diminished in blacks. No significant difference was observed in the hyperemic response to forearm ischemia. CONCLUSIONS: Compared with whites, healthy blacks have reduced vasodilation in response to NO-dependent and -independent stimuli. This difference seems to be related to an attenuation in cyclic nucleotide-mediated vascular smooth muscle relaxation and may play a role in the increased prevalence of hypertension and its complications in blacks.

Acetylcholine↗
PubMed1981

[Serum potassium rise following depolarizing muscle relaxants in immobilized patients (author's transl)].

We investigated the time-course of serum potassium levels after depolarizing muscle relaxants in immobilized patients of our critical care unit. It could be demonstrated that the duration and the degree of immobilisation determines the increase of serum potassium after application of succinylcholine or Imbretil (hexacarbacholine). In burned patients or patients with cord-lesions an earlier increase of serum potassium could be seen than in other immobilized patients. The potassium time-course shows a difference between short acting and long acting muscle relaxants. A block of repolarisation and its possibility of generating is discussed.

Burns↗
PubMed1998

[Measuring muscle relaxation with mivacurium in comparison with mechano- and electromyography].

Based on survey of the literature, methodological problems of electromyographic and mechanomyographic neuromuscular monitoring are presented. Often mechanomyography (MMG) is accompanied by mechanical problems during the registration of the contractions in the operating theatre. In contrast to mechanomyography the registration of electromyographic signals is easier whereas the processing of electromyographic signals is more difficult. In the operating theatre, registration problems can also occur with electromyography (EMG) from artefacts arising from stimulation impulses, high frequency apparatus and alternating current. During neuromuscular monitoring using MMG, a positive drift of the amplitudes of the contractions can be observed, whereas EMG leads to a negative drift of the amplitudes of the action potentials. Both observations can lead to misinterpretation of the degree of neuromuscular block measured by single twitch stimulation during the recovery period. Both the positive and negative drifts can be prevented by single twitch stimulation lasting for up to 10 minutes before the start of the neuromuscular monitoring of the effect of a given dose of a muscle relaxant. Finally, a clinical study of simultaneous registration of the MMG at the M. adductor pollicis and of the EMG at the M. interosseus dorsalis DI under total intravenous anaesthesia using propofol and alfentanil and muscle relaxation with a bolus dose of 75 mg/kg mivacurium is described. During the mechanomyographic studies, a decrease in the preload by an average of 1.2 Newton (N) with a maximum level of 4.0 N occurred. The decrease in preload was less than 25%. The mechanomyographically measured onset time of an ED95 of mivacurium amounted to 3.5 +/- 1.2 minutes on average and the degree of maximum neuromuscular block on average (95.1 +/- 5.6%) tallied very well with the expected value of 95.0%. The electromyographically measured onset time of an ED95 of mivacurium amounted to 4.3 +/- 1.2 minutes on average and the degree of maximum neuromuscular block amounted to only 91.3 +/- 8.1% on average. A comparison of the mechanomyographic values and the electromyographic values leads to the following results: the MMG showed a significantly shorter onset time (p < 0.0001) and a significantly deeper maximum neuromuscular block (p = 0.0004) than the EMG. There were also significant differences between mechanomyographically and electromyographically measured recovery values regarding T1(75) (p = 0.0007), T1(90) (p < 0.0001), TOF0.8 (p = 0.0386) and T1(25-75) (p < 0.0001). On average, an ED95 of mivacurium showed a significantly slower recovery in the mechanomyogram than in the electromyogram.

Adult↗
PubMed1985

Assays for, and cross-reactivities of, IgE antibodies to the muscle relaxants gallamine, decamethonium and succinylcholine (suxamethonium).

Two radioimmunoassays have been developed to detect IgE antibodies to succinylcholine, decamethonium and gallamine in the sera of patients who have experienced life-threatening anaphylactoid reactions following administration of a muscle relaxant drug. They involve the coupling of choline and its ethyl analogue, triethylcholine to activated Sepharose. A high degree of cross-reactivity was shown to occur between drug-reactive IgE antibodies and 6 muscle relaxants as well as choline and triethylcholine. Results suggest that the specificities of the IgE antibodies are directed towards quaternary or tertiary ammonium ions on the drugs that bind the antibodies. Molecular models of these compounds support the structure-activity relationships determined in the inhibition studies.

Antibody Specificity↗
PubMed1986

[Blind nasotracheal intubation in the muscle-relaxed patient].

A modified method of blind nasal intubation, using a muscle relaxant, is described, which has been used in 100 patients with an efficacy of 96%. The risk of suboxygenation was overcome by withdrawing the tube to the epipharynx and ventilating the patient's lungs after each failure to insert the tube in the trachea. The blind nasotracheal intubation of a relaxed patient is to be considered, when orotracheal intubation will be difficult or impossible to achieve, because of anatomic abnormalities or pathologic conditions of the upper respiratory tract. The dangers and complications of the method are discussed.

Adult↗
PubMed1985

[Risk factors in anaphylactoid reactions to muscle relaxants. A retrospective study of 103 cases of shock].

A homogeneous series of 103 cases of shock due to muscle relaxants has been used to identify the risk factors in anaphylactoid shocks due to either true anaphylaxis or to non-specific histamine release. Clinical atopy (asthma) and sub-clinical atopy as shown up by skin tests with mites and pollens, as well as a history of IgE-dependent drug allergy, were present with a significantly greater frequency in the history of patients presenting with anaphylaxis. Abnormal histamine release and reactivity to histamine, as assessed by skin tests with 48/80 and histamine, were often found in those patients who presented with non-specific histamine release induced by muscle relaxants. Whatever the mechanism for the shock, the frequency of spasmophilia was increased. A history of non-immunological intolerance to acetyl salicylic acid and other non-steroid anti-inflammatory drugs was more often found than in the reference drugs was more often found than in the reference population. However, 25% of the patients studied did not have any of these risk factors. Several possibilities of preventing anaphylactoid reactions are given, if one or more of these risk factors are found in the history: a better choice of anaesthetic drugs, in the light of previous anaesthetic protocols, the relief of anxiety by appropriate premedication, antihistamine premedication and the prevention of bronchospasm.

Anaphylaxis↗
PubMed1991

[Effect of isoflurane on muscle relaxation in a patient with myotonic dystrophy].

We did anesthetic management by isoflurane for total thyroidectomy under the neuromuscular transmission monitoring in a patient with myotonic dystrophy. In three patients without neuromuscular disorders, T1 was 85% of control and fade was not observed, while in this case T1 was 40% of the control and TOFR was decreased to 50%. We conclude that isoflurane has a good muscle relaxation effect in this disease and, we could manage without administering any muscle relaxants.

Adult↗
PubMed1980

Effects of nonspecific smooth muscle relaxants on calcium-uptake by microsomal fraction and their inhibitory action in rabbit taenia coli.

Effects of nonspecific smooth muscle relaxants, papaverine and Aspaminol (1,1-diphenyl-3-piperidinobutanol hydrochloride) on Ca-uptake by a microsomal fraction and mechanical activity in the rabbit taenia coli were studied. Papaverine which inhibits cyclic AMP phosphodiesterase increased Ca-uptake by the microsomal fraction in a concentration of 10(-5) M but not in a concentration of 10(-4) M. Potentiation of Ca-uptake by papaverine is considered to be due to the increase of cyclic AMP as the results of the inhibition of phosphodiesterase. Aspaminol which is found to have little inhibitory action on phosphodiesterase activity inhibited Ca-uptake by the microsomal fraction. This inhibition by Aspaminol was abolished by the increase of Ca-concentration in the reaction medium. Non-competitive antihistaminic activity of Aspaminol was considerably reduced by an increase of external Ca-concentration, while the increase of external Ca-concentration slightly decreased antihistaminic activity of papaverine. Furthermore, contraction of KCl-depolarized taenia coli induced by CaCl2 was inhibited competitively by Aspaminol and noncompetitively by papaverine. These results suggest that Aspaminol competes with Ca ions at a surface site of muscle membrane concerned with Ca-uptake process, thus decreasing the supply of Ca ions to the contractile elements and that papaverine may have inhibitory actions on Ca-uptake by the microsomal fraction in addition to stimulatory action which seems to be mediated through cyclic AMP. These actions on Ca-uptake may induce smooth muscle relaxation.

Action Potentials↗
PubMed2000

Propofol without muscle relaxants for conventional or fiberoptic nasotracheal intubation: a dose-finding study.

UNLABELLED: Endotracheal intubation has been performed during the administration of propofol anesthesia without neuromuscular blockade. In this study, we determined the propofol dose required for conventional nasotracheal or for fiberoptic nasotracheal intubation of all patients. Thirty-two patients undergoing maxillofacial surgery were randomly assigned to the conventional (n = 16) or to the fiberoptic (n = 16) intubation group. In both groups, anesthesia was induced by using IV fentanyl and IV titrated propofol according to clinical need (spontaneous respiration rate, verbal response). An endotracheal tube was placed nasally in the pharynx and the vocal cords visualized by using a fiberscope inserted via the tube. In the conventional group, the larynx was visualized additionally with a laryngoscope blade (Miller). In both groups propofol was titrated until the vocal cords opened. Patients were tracheally intubated, and the propofol dose was recorded. In all patients, the trachea could be intubated without the use of muscle relaxants. Considerable interindividual differences of dose requirements were observed. The amount of propofol required in the conventional group was significantly (P < 0.0001) larger (median +/- SD: 2.74 +/- 1.59 mg/kg; range 1.95-7.07 mg/kg) than in the fiberoptic group (1.37 +/- 0.59 mg/kg; 0.72-2.86 mg/kg). Hemodynamics remained stable in all patients. Postintubational hoarseness occurred in three patients of each group. Fiberoptic nasal intubation without a muscle relaxant can be facilitated with significantly smaller and more predictable dosages of propofol than conventional nasal endotracheal intubation. The possibility of titrating the propofol dose under assisted ventilation until the vocal cords open during fiberoptic nasotracheal intubation and the better predictability of the required dose favors the fiberoptic approach. IMPLICATIONS: In this study, contrary to all preceding studies using predefined doses of propofol and opioids, we determined the minimal required propofol dose in combination with fentanyl for conventional or fiberoptic nasotracheal intubation without muscle relaxants.

Adult↗
PubMed2001

[Tracheal intubation without muscle relaxants using propofol and varying doses of fentanyl].

This study was designed to evaluate airway and intubating conditions without muscle relaxants after administration of fentanyl and propofol in 55 patients aged 20-60 years for elective surgery. Patients were randomly assigned to one of four groups to receive fentanyl 0, 2, 3, or 4 micrograms.kg-1, respectively. Three minutes after the administration of fentanyl, propofol (2 mg.kg-1) was given for induction of anesthesia. After the loss of consciousness, laryngoscopy and tracheal intubation, supplemented with topical anesthesia of lidocaine (2 mg.kg-1), were attempted. In control group, without administration of fentanyl, all patients were judged to provide poor intubating conditions. Increasing doses of fentanyl reduced the incidences of movement and persistent coughing on laryngoscopy and intubation in a dose-related manner. However, visualization of the vocal cord was significantly. (P < 0.05) more likely to be impossible in patients in 4 micrograms.kg-1 fentanyl group (40%) compared with patients in 2 micrograms.kg-1 fentanyl group (7%). There were no significant differences among groups receiving fentanyl with respect to vocal cord position. The vocal cords were closed in 26% of patients receiving fentanyl and propofol for intubation. Tracheal intubation without muscle relaxants is not recommended because of the potential unacceptable intubating conditions.

Adult↗
PubMed2001

Probing erectile function: S-(2-boronoethyl)-L-cysteine binds to arginase as a transition state analogue and enhances smooth muscle relaxation in human penile corpus cavernosum.

The boronic acid-based arginine analogue S-(2-boronoethyl)-L-cysteine (BEC) has been synthesized and assayed as a slow-binding competitive inhibitor of the binuclear manganese metalloenzyme arginase. Kinetic measurements indicate a K(I) value of 0.4-0.6 microM, which is in reasonable agreement with the dissociation constant of 2.22 microM measured by isothermal titration calorimetry. The X-ray crystal structure of the arginase-BEC complex has been determined at 2.3 A resolution from crystals perfectly twinned by hemihedry. The structure of the complex reveals that the boronic acid moiety undergoes nucleophilic attack by metal-bridging hydroxide ion to yield a tetrahedral boronate anion that bridges the binuclear manganese cluster, thereby mimicking the tetrahedral intermediate (and its flanking transition states) in the arginine hydrolysis reaction. Accordingly, the binding mode of BEC is consistent with the structure-based mechanism proposed for arginase as outlined in Cox et al. [Cox, J. D., Cama, E., Colleluori D. M., Pethe, S., Boucher, J. S., Mansuy, D., Ash, D. E., and Christianson, D. W. (2001) Biochemistry 40, 2689-2701.]. Since BEC does not inhibit nitric oxide synthase, BEC serves as a valuable reagent to probe the physiological relationship between arginase and nitric oxide (NO) synthase in regulating the NO-dependent smooth muscle relaxation in human penile corpus cavernosum tissue that is required for erection. Consequently, we demonstrate that arginase is present in human penile corpus cavernosum tissue, and that the arginase inhibitor BEC causes significant enhancement of NO-dependent smooth muscle relaxation in this tissue. Therefore, human penile arginase is a potential target for the treatment of sexual dysfunction in the male.

Animals↗
PubMed1990

Negative pressure pulmonary oedema: a potential hazard of muscle relaxants in awake infants.

We report two cases of healthy infants who were given an IV intubating bolus of a nondepolarizing muscle relaxant (0.1 mg.kg-1 vecuronium) at the beginning of an inhalational induction of anaesthesia. Shortly after the introduction of low concentrations of gaseous agents, both infants exhibited airway obstruction although inspiratory muscle activity was still vigorous. The airway obstruction was due to approximation of the tongue to the posterior pharyngeal wall, and was easily corrected by insertion of an oral airway. The infants immediately exhibited fulminant pulmonary oedema, which responded to conventional therapy. It is postulated that paralysis of glossal muscles occurred prior to diaphragmatic paralysis, creating upper airway obstruction while preserving inspiratory muscle activity. This can rapidly lead to negative pressure pulmonary oedema in the small infant. Meticulous attention to the maintenance of an unobstructed upper airway is required if muscle relaxants are administered to the awake infant.

Airway Obstruction↗
PubMed1993

The muscle relaxant properties of Portulaca oleracea are associated with high concentrations of potassium ions.

The juice and aqueous extracts from the plant Portulaca oleracea have been used in West Africa for a variety of medical purposes, and extracts were previously shown to have muscle relaxant properties on isolated nerve-muscle preparations. We have attempted to characterise the components responsible for this activity. Ethanolic extracts caused an initial augmentation of twitch height in chick biventer cervicis preparations and then blockade which appeared to be mediated by an action directly on muscle fibres rather than on neuromuscular transmission. Solvent fractionation of the crude ethanolic extract followed by bioassay on the chick biventer cervicis preparation showed that muscle paralysis increased with increasing polarity: i.e. water fraction > butanol > ethyl acetate approximately equal to crude extracts. These fractions contained 28%, 18%, 12.2% and 9%, respectively, of potassium by weight of dried extract. Similar concentrations of KCl reproduced the same effect as the extracts on muscle activity, and when the most active fraction (water fraction) was desalted, it had no neuromuscular activity even at 10 times higher concentration than used previously. We conclude that the neuromuscular activity of extracts of Portulaca oleracea is caused by high concentrations of potassium ions.

Animals↗
PubMed1991

[Effects of muscle relaxant E-0646 on human stretch reflex and responses].

The experiment examined the effects of a muscle relaxant E-0646 on short latency stretch reflex (SLR) and long latency stretch responses (LLRs) of lower leg muscles in 5 healthy male subjects, aged 24-41 years. An AC servomotor produced an ankle rotation of comfortably seated subjects in the direction to stretch the triceps surae muscle for the SLR and the tibialis anterior muscle for the LLRs. Following control measurements, after the oral administration of 50, 100, 150, and 300 mg of E-0646, the SLR and LLRs were recorded every 2 hours for 4 or 6 hours with simultaneous blood sampling to measure E-0646 plasma levels. Electromyograms (EMGs) of the soleus and tibialis anterior muscles were recorded with surface electrodes on each muscle belly. A precision potentiometer was used to measure the ankle angle. The soleus SLR, evoked by a torque pulse (7 msec duration) of one of 5 different amplitudes, decreased 2 hours after the 300 mg administration. A SLR decrease was also found in a simple relationship between the integrated SLR EMG and the angular velocity at 20 msec after the torque onset, in which the slope and intercept of the relationship changed. The plasma E-0646 level roughly correlated with the SLR decrease. No significant change of the SLR was observed when dosage was less than 150 mg. The LLRs of the tibialis anterior muscle were tested under the instruction "resist when perturbed" during a weak isometric contraction against a constant plantar flexion torque.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Pharmacodynamic modeling of muscle relaxants: effect of design issues on results.

BACKGROUND: Pharmacodynamic studies of muscle relaxants use different dosing regimens (such as administration by bolus vs. infusion and doses that produce complete vs. incomplete paralysis). The authors used published data to evaluate the effect of modeling assumptions on pharmacodynamic estimates. METHODS: The authors used a pharmacokinetic-pharmacodynamic dataset in which patients received cisatracurium, 75 or 300 microg/kg (1.5 or 6 x ED95), to generate plasma concentration (Cp) and twitch depression (effect) curves. They then evaluated the impact of the following: assuming that Cp decreased monotonically versus increasing initially before decreasing monotonically; misrecording effect data by 6 s or less; and doses targeting incomplete versus complete paralysis. Parameters evaluated were the steady state Cp depressing twitch tension 50% (C50) and the rate constant for equilibration between plasma and effect site concentrations (k(e0)). RESULTS: With the large dose, increasing the time at which Cp peaked from 0.0 to 1.5 min decreased C50 and increased k(e0) markedly; with the small dose, changes in both were small. Misrecording the timing of effect had a larger impact with the large dose compared with the small dose. Doses smaller than ED50 or those producing prolonged, complete twitch depression yielded biased and variable estimates. CONCLUSION: The erroneous assumption that Cp decreases monotonically after bolus administration affects accuracy of pharmacodynamic estimates with doses producing rapid, complete twitch depression. Other errors (e.g., misrecording the time of drug administration) impact on pharmacodynamic estimates, particularly with large doses. The authors' findings suggest that investigators performing neuromuscular (and other) pharmacodynamic studies should carefully consider the impact of study design on their parameter estimates.

Artifacts↗
PubMedDate not supplied

Silperisone: a centrally acting muscle relaxant.

Silperisone is a tolperisone like organosilicon compound with centrally acting muscle relaxant properties. Studies in mice showed that silperisone may have less propensity to cause CNS depressant or motor side effects than tolperisone or other antispastic drugs. In cats and rats, silperisone was an effective suppressant of monosynaptic and polysynaptic spinal reflexes and decerebrate rigidity. Its suppressant effect on the spinal reflexes was also demonstrated in the isolated hemisected rat spinal cord in vitro. The in vivo potency and efficacy of silperisone by i.v administration were similar to those of tolperisone and eperisone. However, in cats by intraduodenal administration and in mice by oral administration its duration of action was much longer and its functional bioavailability much higher than of the other two drugs. With regard to its profile of actions silperisone was similar to tolperisone with minor differences. The most striking difference was in pontine facilitation and bulbar inhibition of the patellar reflex. Tolperisone depressed both, whereas silperisone inhibited only the former. The mechanism underlying the spinal reflex depressant effects of silperisone involves the blockade of voltage gated neuronal sodium and calcium channels leading to a decreased release of excitatory transmitter and reduced neuronal excitability. In addition, silperisone has potassium channel blocking effect, which is stronger than that of tolperisone. Silperisone is absorbed rapidly and is extensively metabolized in rats. However, its metabolism in dogs and particularly in humans is much less extensive. The elimination half-life of silperisone in humans is 12 to 16 h, so that it can be administered once or twice daily. Phase I clinical studies with silperisone at doses up to 150 mg/day failed to detect any adverse effects at plasma concentrations considered to be effective in the preclinical tests. These findings suggested that silperisone might be a useful antispastic drug. However, findings in chronic animal toxicity studies led to the discontinuation of silperisone's development.

Animals↗