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PubMed2001

Estrogen protects against hypertension in the spontaneously hypertensive rat, but its protective mechanism is unrelated to impaired arterial muscle relaxation.

OBJECTIVES: To determine if estrogen acutely and directly alters arterial muscle relaxation, if estrogen is responsible for gender dichotomy in hypertension, and if arterial muscle from female spontaneously hypertensive rats (SHR) is slow to relax as is muscle from male SHR compared with arterial muscle of normotensive Wistar-Kyoto rats (WKY). METHODS: Relaxation rates of isometrically contracted arterial muscle from male rats were measured before and after addition of beta-estradiol. Blood pressure (BP) was monitored in intact male and female SHR and WKY and in ovariectomized and estrone-treated ovariectomized SHR and WKY. Relaxation rates of maximum isometric contractions of arterial muscle excised from male SHR and WKY and female SHR and WKY with varying chronic estrogen status were measured. RESULTS: Beta-estradiol had no direct, acute effect on arterial muscle force or relaxation. Intact and estrone-implanted SHR females had significantly lower BP than males. Ovariectomized SHR developed high BP equivalent to that of males. Arterial relaxation was slower in both male and female SHR compared with WKY. CONCLUSIONS: Estrogen lowers BP in female SHR. Strain differences in relaxation rates are independent of gender and estrogen status. Estrogen has no effect on arterial muscle relaxation, suggesting another mechanism for the protective effect of estrogen in hypertension.

Analysis of Variance↗
PubMed2003

Competition between acetylcholine and a nondepolarizing muscle relaxant for binding to the postsynaptic receptors at the motor end plate: simulation of twitch strength and neuromuscular block.

UNLABELLED: The goal of the study was to simulate twitch strength and neuromuscular block produced by nondepolarizing muscle relaxants. METHODS: In the proposed model, affinities of the two binding sites at a single postsynaptic receptor for acetylcholine (A) and the muscle relaxant (D) define the formation of three complexes with A only, three complexes with D only, and two complexes with both A and D. Twitch strength was postulated to be a function of the receptors with both binding sites occupied by A, and two constants. Neuromuscular block (NMB) was calculated from NMB = 1-twitch. RESULTS: Stimulus-induced release of A results in rapid, but transient, changes in the concentrations of free A, the eight complexes, and the unoccupied receptors. Muscle relaxants that display either a congruous or an inverse pattern of affinities for the binding sites relative to those of A produce NMB vs. [D] curves with slightly different slopes but markedly different estimates for IC50. Depending on the number of activated receptors at the end plates of muscle fibers, the simulations represent the distributions of contracting fibers in a whole muscle. CONCLUSION: Simulations of competition between A and D for binding to two sites at a receptor reveal that the potencies of muscle relaxants, defined by IC50, and the slopes of the NMB vs. [D] curves depend on (1) the affinities of D for the two binding sites, (2) the orientation of the affinities relative to those of A, and (3) the affinities of A for the same two sites.

Acetylcholine↗
PubMed1985

Muscle relaxant action of excitatory amino acid antagonists.

Antagonists of neuronal excitation induced by dicarboxylic amino acids were tested in genetically spastic rats of the Han-Wistar strain. These animals exhibit an increased muscle tone which can be measured as a spontaneous tonic activity in the electromyogram of the gastrocnemius-soleus muscle. Compounds that block excitation due to N-methyl-D-aspartic acid reduced the spontaneous activity measured in the electromyogram in a dose-related manner. The most potent compounds, 2-amino-7-phosphonoheptanoic and kynurenic acids were effective muscle relaxants when given either intraperitoneally or intracerebroventricularly. 2-Amino-5-phosphonopentanoic acid possessed much weaker muscle relaxant activity, while L-glutamic acid diethylester was inactive by either route. The results suggest that blockade of N-methyl-D-aspartic acid receptors results in a myorelaxant effect. Specific antagonists of excitation at N-methyl-D-aspartic acid receptors may provide a new class of muscle relaxants.

2-Amino-5-phosphonovalerate↗
PubMed2001

The effect of sildenafil on corpus cavernosal smooth muscle relaxation and cyclic GMP formation in the diabetic rabbit.

Sildenafil, a type V phosphodiesterase inhibitor, enhances smooth muscle relaxation in normal human and rabbit corpus cavernosum. We investigated the in vitro effects of sildenafil on non-adrenergic, non-cholinergic and nitric oxide (NO)-mediated cavernosal smooth muscle relaxation in diabetic rabbits, since alterations in this pathway are recognised in diabetic erectile dysfunction. Diabetes mellitus was induced in male New Zealand White rabbits with alloxan. Cavernosal strips from age-matched control, 3- and 6-month diabetic animals were mounted in organ baths. Relaxation responses to electrical field stimulation (1-20 Hz) or sodium nitroprusside (10(-8)-10(-4) M) were assessed in the absence and presence of sildenafil (10(-8) and 10(-7) M). The effect of sildenafil on cGMP formation by the corpus cavernosum was also assessed following stimulation with sodium nitroprusside, A23187 and acetylcholine. Sodium nitroprusside-stimulated relaxations were significantly (P<0.03) impaired in the corpus cavernosum from both diabetic groups, (IC(50)=4.6 x 10(-6) M following 3 months of diabetes mellitus and 4.0 x 10(-6) M following 6 months of diabetes mellitus; compared to 7.5 x 10(-7) M for pooled age-matched controls). Sildenafil (10(-7) M) significantly enhanced sodium nitroprusside-stimulated relaxation in control (P<0.05) and diabetic groups (P<0.03). Electrical field stimulation-mediated relaxations of the corpus cavernosum were significantly impaired after 6-month diabetes mellitus and enhanced by sildenafil (10(-8) M). cGMP formation by the diabetic corpus cavernosum was impaired significantly, but restored towards normal by sildenafil. We suggest that the impairment of NO-mediated relaxation of the corpus cavernosum reflect, at least in part, a defect in guanylyl cyclase activity. These findings support the use of sildenafil as an effective, orally administered, treatment for diabetic erectile dysfunction.

Acetylcholine↗
PubMed1992

On central muscle relaxants, strychnine-insensitive glycine receptors and two old drugs: zoxazolamine and HA-966.

Zoxazolamine is in the centrally-acting muscle relaxant class of drugs, which reportedly act by decreasing CNS interneuronal activity. These drugs, but not anxiolytics, decrease dopaminergic turnover and induce a pacemaker-like discharge pattern in dopaminergic neurons. A mechanism for these effects was not found in previous reports. We observed that (+)-HA-966, an inhibitor of the glycine modulatory site on the NMDA receptor, has a similar effect on dopaminergic impulse flow, which suggested that this may be the possible site of action of classical muscle relaxants. However, a competitive antagonist of NMDA receptors, NPC-12626, had little effect on impulse flow. Binding of 20 nM [3H]-glycine to cortical synaptosomal membranes was inhibited by (+)-HA-966, IC50 = 3.16 microM, but only poorly by zoxazolamine, IC50 V 474 microM, and chlorzoxazone, a related drug, caused no displacement. The drugs were then tested for protection from amphetamine neurotoxicity. Neither 50 mg/kg zoxazolamine nor 30 mg/kg (+)-HA-966 prevented (+)-amphetamine (0.1 mmol/kg plus 10 mg/kg iprindole) depletion of striatal dopamine (DA), but 3.0 mg/kg of MK-801, a non-competitive NMDA receptor antagonist, did protect DA content. Since baclofen induces a regular firing rate in DA neurons, zoxazolamine and (+)-HA-966 were tested for displacement of 10 nM [3H]-1-baclofen from cortical synaptosomal GABAb receptors, but were ineffective. Thus, the effects of these muscle relaxants on DA neurons are mediated by a mechanism other than strychnine-insensitive glycine or GABAb receptors.

Amphetamine↗
PubMed1985

[Potentiation of the effect of non-depolarizing muscle relaxants by acylaminopenicillins. Studies on the example of vecuronium].

In a prospective controlled clinical study interactions between nondepolarizing muscle relaxants and acylaminopenicillins were investigated electromyographically. Six patients in each group received either apalcillin, azlocillin, mezlocillin or piperacillin during the operation. Muscle relaxation was maintained using the short acting nondepolarizing relaxant vecuronium, which shows no cumulative effect within clinical dosages. The intra-individual comparison with the control period (100%) showed a significant prolongation of the duration of action after a fixed dose of vecuronium. The mean increase was +26% following apalcillin, +46% after piperacillin, +38% following mezlocillin and +55% following azlocillin. The shortest time of the control periods was 8.6 min and the maximum time was 32.6 min. We also found a significant depression of the EMG-response. No significant differences could be detected between the four antibiotics. The method described here has proven to be sensitive enough to detect clinically relevant interactions with muscle relaxants. As a result of our study, caution seems to be necessary if acylaminopenicillins are administered in the early postoperative period.

Adult↗
PubMedDate not supplied

[Intracranial pressure response during secretion aspiration after administration of a muscle relaxant].

UNLABELLED: Aspiration of secretions is a usual nursing technique in patients undergoing mechanical ventilation that may be the cause of increased Intracranial Pressure (ICP). OBJECTIVE: This study aims to evaluate the repercussion of a muscle relaxant on ICP with secretion aspiration. METHOD: Clinical trial using the same patient as case and control, performing two endotracheal aspirations in each patients, on of them after administration of a muscle relaxant (Cis-Atracurium) and another no. The bolus administration of the relaxant in the first or second aspiration was done randomly. Thirteen patients with intraparenchymatous ICP measurement catheter were studied within the first 36 hours post-placement and with sedoanalgesia for a score of 6 on the Ramsay scale. ICP and CPP were measured before, during and after each aspiration. STATISTICAL METHOD: SPSS 11.0 program was used. Data analysis by Student's t test for paired data. Statistical significance level accepted was 95%. RESULTS: On comparing the cases in which muscle relaxant was administered with those in which it was not administered, statistically significant differences were found in the ICP and CCP values during secretion aspiration. CONCLUSIONS: According to the data obtained in the study, a lower increase of ICP was observed during secretion aspiration in those cases in which muscle relaxant was administered prior to the aspiration.

Adolescent↗
PubMed1997

In vitro studies on the interactions of beta2-adrenoceptor agonists, methylxanthines, Ca2+-channel blockers, K+-channel openers and other airway smooth muscle relaxants in isolated guinea-pig trachea.

Pharmacodynamic interactions in vitro between different types of airway smooth muscle relaxants were systematically and quantitatively evaluated by using a new methodological technique. Relaxant concentration-effect curves for terbutaline, theophylline, cromakalim, sodium nitroprusside and isradipine were obtained in isolated guinea-pig trachea contracted by histamine (1 microM). The effects of three different fixed concentrations of each airway smooth muscle relaxant were initially attained and concentration-effect curves for combinations with increasing concentrations of either one of the other relaxants were produced. Based on pharmacodynamic parameters obtained by non-linear regression analysis of experimental data for the relaxants alone theoretical concentration-effect curves for predicted additive interaction were constructed by using the isobolic method. Synergistic (over-additive) interaction was defined as existing when data points and derived pharmacodynamic parameters obtained with combinations of the relaxants showed statistically significant deviation from the predicted additive interaction curve and its functional parameters. Significant synergistic interaction with terbutaline was found for both theophylline (70 or 200 microM), cromakalim (0.1, 0.3 or 1 microM), sodium nitroprusside (30 or 100 nM) and isradipine (1, 3 or 10 nM). Theophylline showed synergistic interaction with cromakalim (0.1, 0.3 or 1 microM), sodium nitroprusside (10 nM) and isradipine (1, 3 or 10 nM). Interactions between cromakalim and sodium nitroprusside (10, 30 or 100 nM) were also synergistic, whereas cromakalim and isradipine (1, 3 or 10 nM) produced only additive interaction. Possible mechanisms underlying the interactions are discussed on basis of existing knowledge with special regards to phosphodiesterase isoenzymes, K+ and Ca2+ channels.

Adrenergic beta-Agonists↗
PubMedDate not supplied

In vitro comparison of the neuromuscular antinicotinic and intestinal antimuscarinic effects of different nondepolarizing muscle relaxants.

The postsynaptic antimuscarinic properties of different nondepolarizing muscle relaxants were compared with their postsynaptic antinicotinic effect. d-Tubocurarine, pipecuronium and vecuronium were the most selective antagonists on postsynaptic nicotinic receptors. Gallamine, diadonium and Duador (RGH-4201) had relatively greater effect on postsynaptic muscarinic receptors. Therefore, much less side effect is expected to occur when pipecuronium, d-tubocurarine or vecuronium are used.

Animals↗
PubMed1984

A specific benzodiazepine antagonist CGS 8216 reverses the muscle relaxant effect of diazepam but not that of phenobarbitone.

The muscle relaxant effects of diazepam and phenobarbitone were studied in mutant Han-Wistar rats which exhibit spontaneous tonic activity in the electromyogram of the gastrocnemius-soleus muscle. Diazepam and phenobarbitone significantly and dose- relatedly reduced the spontaneous activity measured in the electromyogram. The benzodiazepine receptor antagonist CGS 8216 reversed the depressant effect of diazepam but not that produced by phenobarbitone. The results add further support to the suggestion that CGS 8216 may be useful to investigate the effects modified by benzodiazepine receptors in vivo.

Animals↗
PubMedDate not supplied

The effects of music and muscle relaxation on patient anxiety in a coronary care unit.

OBJECTIVE: To test the efficacy of music and muscle relaxation techniques in reducing the anxiety of patients admitted to a coronary care unit with ischemic heart disease. DESIGN: Randomized, controlled trial. SETTING: Seven-bed coronary care unit of an Australian tertiary care hospital. PATIENTS: Fifty-six patients admitted to a coronary care unit with unstable angina pectoris or acute myocardial infarction. OUTCOME MEASURES: Psychologic (State Trait Anxiety Inventory, Hospital Anxiety and Depression Scale, Linear Analogue Anxiety Scale) and physiologic (systolic and diastolic blood pressure and heart rate) variables were measured as indicators of anxiety. INTERVENTION: Two or three 30-minute sessions of audiotape interventions were conducted with portable tape players with headphones. The two intervention tapes consisted of light classical music and verbal instructions for muscle relaxation. RESULTS: With analysis of variance procedures, the null hypotheses were supported. No significant differences (p < 0.05) between groups were demonstrated for the psychologic or physiologic variables; that is, no significant reductions in anxiety were achieved for patients using music or muscle relaxation interventions when compared with the control group. The effect size of the interventions on the outcome measures was 0.19 to 0.22, indicating a small effect. Resultant power was at a low level. CONCLUSIONS: These results differ from those of similar studies but may be related to the high probability of a type II error. Further investigation with longer intervention sessions and larger sample sizes is indicated. Similar studies should incorporate power analysis when reporting their results.

Angina, Unstable↗
PubMed2006

Effects of age and timing of augmented feedback on learning muscle relaxation while performing a gross motor task.

OBJECTIVE: To examine the combined effect of age and timing of augmented feedback on learning muscle relaxation. Performing a gross motor task, subjects had to lower their trapezius muscle activity using the electromyographic signal as visual myofeedback. DESIGN: Healthy subjects (16 young adults: 20-35 yrs; and 16 older adults: 55-70 yrs) were randomly assigned to one of two timing conditions of myofeedback: concurrent (feedback was provided immediately during the trial) and terminal (feedback was provided delayed after the trial) condition. RESULTS: The results indicated that young adults had a higher level of motor performance (i.e., lower muscle activity) compared with older adults when myofeedback was provided. These effects persisted during short- (after 10 mins) and long-term retention (after 1 wk) when no myofeedback was provided. In contrast to young adults, older adults did not improve their performance throughout the experiment. There were no interactions of age with the timing conditions of myofeedback during acquisition and retention. CONCLUSIONS: Either timing condition of augmented feedback was equally helpful to young adults, whereas neither was helpful for older adults in learning muscle relaxation.

Adult↗
PubMed1989

[Centrally acting muscle relaxant effect of phthalides (ligustilide, cnidilide and senkyunolide) obtained from Cnidium officinale Makino].

The present study was carried out to elucidate a centrally acting muscle relaxant effect of chloroform soluble fraction and its component, namely, ligustilide, cnidilide and senkyunolide obtained from the rhizome of Cnidium officinale Makino. These three compounds were isolated from the chloroform soluble fraction by column chromatography on silica gel. The centrally acting muscle relaxant effect was investigated on the crossed extensor reflex in anesthetized rats and these samples were suspended in 0.5% carboxymethyl cellulose solution and administered i.p. These three compounds as well as the chloroform soluble fraction depressed the reflex response. The depressive potencies among them were almost the same and their potencies were also the same or somewhat weaker as that of mephenesin. As a curare-like action was not observed, a muscle relaxation induced by these phthalide compounds is considered to be due to central origin.

4-Butyrolactone↗
PubMed1982

Modification of calcium fluxes by dimethyl sulfoxide and 2-butoxyethanol in sarcoplasmic reticulum vesicles: a possible mechanism for skeletal muscle relaxation induced by dimethyl sulfoxide.

In order to investigate the mechanism of skeletal muscle relaxation induced by dimethyl sulfoxide, 2-butoxyethanol and dimethyl sulfoxide were examined for their effects on 1) Ca2+ uptake into and efflux from sarcoplasmic reticulum vesicles prepared from rabbit fast skeletal muscle and crayfish tail muscle by the murexide method, 2) ATPase activities of rabbit reticulum vesicles, 3) the isolated phrenic nerve-diaphragm preparation of the rat and 4) crayfish opener muscle preparation. Ca2+ efflux rate from rabbit reticulum vesicles was markedly decreased with increasing concentrations (5-20% v/v) of dimethyl sulfoxide without affecting the maximum Ca2+ uptake by the reticulum. 2-Butoxyethanol showed quite contrary effects. Dimethyl sulfoxide strongly inhibited the activity of basal ATPase rather than of Ca2+-dependent ATPase. 2-Butoxyethanol did not significantly inhibit the activity of basal ATPase, but markedly increased Ca2+-dependent ATPase activity. Antagonisms between dimethyl sulfoxide and caffeine were demonstrated either in contractions of crayfish opener muscles or in the Ca2+ release from crayfish sarcoplasmic reticulum vesicles. These results indicate a possibility that dimethyl sulfoxide reversibly induces skeletal muscle relaxation mainly in the sarcoplasmic reticulum by means of decreasing the rate and the amount of Ca2+ release from the reticulum.

Adenosine Triphosphatases↗
PubMedDate not supplied

The synergistic effect of two different nondepolarizing muscle relaxants on intraocular pressure.

STUDY OBJECTIVES: To evaluate the synergistic effect of neuromuscular blockade, produced by administering a priming dose of d-tubocurarine before or after pancuronium bromide, on endotracheal intubating conditions, intraocular pressure (IOP), and hemodynamic changes 1 minute following injection of intubating doses. To compare the results with equipotent doses of the individual muscle relaxants administered as a single bolus dose or in divided doses. DESIGN: Randomized study. SETTING: University medical center. PATIENTS: Ninety ASA physical status I and II inpatients (45 males, 45 females) assigned to one of six comparable groups (A-F). INTERVENTIONS: One hour after premedication, either normal saline (Groups A and B) or a priming dose of either d-tubocurarine (Groups C and F) or pancuronium (Groups D and E) was given intravenously (IV). Three minutes later, anesthesia was induced with 6 mg/kg of 2.5% thiopentone i.v. Then an intubating dose of pancuronium (Groups A, C, and E) or d-tubocurarine (Groups B, D, and F) was administered. The total dose given was equal to d-tubocurarine 0.4 mg/kg or pancuronium 0.07 mg/kg. Patients were intubated 1 minute after injection of an intubating dose of either relaxant. MEASUREMENTS AND MAIN RESULTS: IOP was measured with a Perkins applanation tonometer and blood pressure (BP) by a sphygmomanometer. Heart rate was derived from the electrocardiogram. Intubating conditions were scored according to given intubation criteria. Measurements were obtained at different times before and after intubation. In those patients given only one muscle relaxant for intubation either divided into priming and intubating doses or preceded by normal saline (Groups A, B, E, and F), there was a significant increase in IOP in response to intubation as compared with baseline (p < 0.05). In contrast, when d-tubocurarine was used as the priming drug for pancuronium blockade (Group C), IOP was significantly reduced in response to intubation, despite a concomitant increase in BP (p < 0.05). No significant change in IOP was observed when pancuronium was used as the priming drug for d-tubocurarine blockade (Group D). Although good to excellent intubating conditions were reported in Groups C and D, poor intubating conditions were reported when the priming muscle relaxant was the same as the relaxant used to intubate. CONCLUSIONS: A smooth, rapid-sequence intubation with a concomitant reduction in IOP as required for open-eye, full-stomach patients can be achieved with a judicious mixture of nondepolarizing muscle relaxants as described for d-tubocurarine and pancuronium in Groups C and D.

Adult↗
PubMed1998

[Cleavage and biotransformation of the central muscle relaxant chlormezanone].

Chlormezanone, a chiral centrally acting muscle relaxant, will be cleaved at its S-C-1 bond by an autoprotolytic process. The optimum of chemical stability exists between pH 2 up to pH 9 with a maximum at pH 7.4. The plasma half life at 37 degrees C is 76 h. Enzymes do attack the products of cleavage namely 4-chlorobenzaldehyde and 2-carboxyethane-sulfinic-acid-N-methyl-amide. The main metabolite in urine is 4-chlorohippuric acid in the range of up to 70% of the oral administered dose to humans. No cytochrome P-450 is engaged in the cleavage of the S-C-bond.

Biotransformation↗
PubMed1992

The pharmacological properties of CS-722, a newly synthesized centrally acting muscle relaxant.

The pharmacological properties of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized, centrally acting muscle relaxant, were studied in rats. The drug CS-722 reduced the radio frequency decerebrate rigidity in a dose-dependent manner (25-100 mg/kg, p.o.); it inhibited the increase in discharges from Ia afferent fibers, gamma-motor activity, which was induced by stimulation of the reticular formation. The compound, however, showed no effect on the basal discharge of Ia afferent fibers. The polysynaptic reflex was depressed by CS-722, with less influence on the monosynaptic reflex in intact and spinal preparations and CS-722 did not prolong thiopental-induced sleeping time. In rats anesthetized with halothane, CS-722 did not affect the electroencephalogram (EEG) arousal response, which was elicited by stimulation of the reticular formation. The results of this study suggest that CS-722 can exert a muscle relaxant action, at a dose range at which depression of the ascending reticular activating system was negligible. The results also suggest that depressions of the gamma-motor system and the polysynaptic reflex may contribute to the muscle relaxant action of CS-722.

Animals↗
PubMedDate not supplied

[Effect of muscle relaxation in hypertensive patients].

The efficacy of muscle relaxation in the treatment of hypertension has been described by several authors. Our experience with this type of technique is analyzed in this report. The clinical histories of 38 individuals who have taken part in the relaxation program since the end of 1984 (relaxation group: RG) with at least 6 months of follow up, have been reviewed. For each RG patient, two sex, age, and initial diastolic blood pressure (DBP) matched controls were found, obtaining thus a control group (CG) consisting of 70 hypertensive patients who were not participating in any relaxation program. The final efficacy of the program was evaluated recording the systolic blood pressure (SBP), the DBP, and heart rate (HR) 6 and 12 months after the initiation of the program also considering the drop outs and the need of drugs (evaluated with a therapeutic index: TI). There were no differences in the initial parameters between the two groups except for the TI (uncontrollable variable) which was higher in the RG. The final values in the RG showed a slightly lower blood pressure (RG = 135.2/86.9 mm Hg; CG = 139.4/90.4 mm Hg, p = 0.082 for the DBP) as well as a lower number of drop outs (RG = 18.4%); CG = 32.9%, p less than 0.1). 10 patients in the RG while none in the CG were medically discharged. (p = 0.000). The only significant difference found was the increase in TI in the CG (p = 0.000), while the increase observed in the RG was not statistically significant.

Adult↗