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At least 667 records · Page 37Linked to original sources
PubMed1984

System and organ-selectivity of smooth muscle relaxants on in vitro spontaneously contracting preparations.

The effects of verapamil, papaverine and octylonium bromide on amplitude and frequency of spontaneous contractions of rabbit duodenum and rat colon, portal vein and right atria have been investigated. Myogenic nature of spontaneous contractions was demonstrated by their resistance to tetrodotoxin (100 micrograms/ml) and hexamethonium (10(-4) M). Verapamil (10(-7) - 5 X 10(-6) M) reduced, in a concentration-dependent manner, amplitude and frequency of spontaneous contractions with a certain degree of selectivity for duodenal preparations. Automaticity of rat right atria was affected by concentrations of verapamil higher than those required to modify automaticity of intestinal preparations. Papaverine (3 X 10(-6) - 3 X 10(-4) M), was almost equipotent in reducing the amplitude of spontaneous contractions of each preparation but inhibited the frequency of contractions in the following order: colon greater than duodenum greater than atrium. Octylonium bromide (10(-6) - 10(-4) M) was characterized by its greater effectiveness in reducing frequency and amplitude of spontaneous contractions of rat colon as compared to the other preparations. All three smooth muscle relaxant drugs, in spite of concentration-related reduction in amplitude, determined a parallel enhancement of frequency of spontaneous contractions in rat portal vein. Differences in drug selectivity are discussed in terms of different roles played by various Ca++-dependent processes (which constitute the cellular target of action of these smooth muscle relaxant drugs) in the genesis of frequency and amplitude of myogenic contractions in the various preparations.

Animals↗
PubMed1988

Inhibitory effects of a new, potent, centrally acting muscle relaxant, (4S,5R)-4-(2-methylpropyl)-3-[3-(perhydroazepin-1-yl)propyl]-5- phenyl-1,3-oxazolidin-2-one (NC-1200) on micturition contractions of the bladder in rats.

The effect of the centrally acting muscle relaxant, (4S,5R)-4-(2-methylpropyl)-3-[3-(perhydroazepin-1-yl)propyl]-5- phenyl-1,3-oxazolidin-2-one (NC-1200) on micturition contractions of the urinary bladder was tested in anesthetized rats with the intention of using it clinically to depress vesical micturition contractions. Rhythmic micturition contractions of the bladder were produced by expanding a balloon inserted in the bladder. Efferent nerve activity of the pelvic and hypogastric branches of the bladder was recorded. Both the vesical micturition contractions and the rhythmic burst discharges of the pelvic efferent nerve were inhibited by the i.v. administration of NC-1200 (1-10 mg/kg) in a dose-dependent manner. Hypogastric efferent nerve activity and ganglionic synaptic transmission from the pelvic preganglionic neurons to their postganglionic neurons innervating the bladder were not influenced significantly by the i.v. administration of NC-1200. No inhibitory effect on vesical smooth muscle was observed. From these results we concluded that NC-1200 inhibits the micturition contraction by inhibiting pelvic efferent nerve activity and that this inhibitory effect of NC-1200 originates mainly in the central nervous system.

Animals↗
PubMed1998

cGMP-independent mechanism of airway smooth muscle relaxation induced by S-nitrosoglutathione.

This study tested the hypothesis that the NO donor S-nitrosoglutathione (GSNO) relaxes canine tracheal smooth muscle (CTSM) in part by a cGMP-independent process that involves reversible oxidation of intracellular thiols. GSNO caused a concentration-dependent relaxation in ACh-contracted strips (EC50 approximately 1.2 microM) accompanied by a concentration-dependent increase in cytosolic cGMP concentration ([cGMP]i). The soluble guanylate cyclase inhibitor methylene blue prevented the increase in [cGMP]i induced by 1 and 10 microM GSNO, but isometric force decreased by 10 +/- 4 and 55 +/- 3%, respectively. After recovery of [cGMP]i to baseline, GSNO-induced relaxation persisted during continuous ACh stimulation. Dithiothreitol caused a rapid recovery of isometric force to values similar to those obtained with ACh alone in these strips. We conclude that GSNO relaxes CTSM contracted by ACh in part by oxidation of intracellular protein thiols.

Acetylcholine↗
PubMed1993

Efficacy of abbreviated progressive muscle relaxation training: a quantitative review of behavioral medicine research.

A quantitative review was undertaken of recent research in which abbreviated progressive muscle relaxation training (APRT) was used as an intervention for psychophysiological and stress-related disorders. The strength of association between APRT and outcome measures was calculated for 29 experiments published after 1980. The average effect size across all experiments was moderate (r = .40). Moreover, for experiments that included a follow-up assessment, a similar effect size was noted at the first follow-up (r = .43). Additionally, experiments that used a prospective design (i.e., analyzed change) detected a stronger effect for APRT than those that used a cross-sectional design (i.e., compared groups). APRT was most strongly associated with improvement in experiments that delivered APRT on an individual basis and provided recipients with training tapes. Moreover, the treatment duration and number of sessions positively influenced the strength of association.

Arousal↗
PubMed1982

Stable muscle relaxation during abdominal surgery using combined intravenous bolus and demand infusion: clinical appraisal with ORG NC45.

In order to obtain stable muscle relaxation for intra-abdominal operation, a continuous demand perfusion of ORG NC45 was administered following a loading dose of 0.07 mg . kg-1. The patients had previously been anaesthetized with methohexitone, fentanyl and nitrous oxide. The perfusion rate of ORG NC45 was regulated so that the mechanical muscular response of the adductor pollicis following a supra-maximal stimulation of the ulnar nerve was maintained at 10 per cent of its initial value. The level of relaxation thus obtained was always adequate for the surgeons. During the course of the operation the requirement for more relaxant decreased progressively, becoming stable after one half hour. Nevertheless, during stable administration, individual variations were quite marked, being 44 to 483 micrograms/M2 BSA/10 min (average 225 micrograms/M2 BSA/10 min). The duration of the infusion varied from 60 to 107 minutes (average 103 minutes). After its termination the time taken from recovery varied between 3 and 82 minutes (average 27 minutes). Having regained a single twitch height of 75 per cent patients awoke rapidly after the administration of nitrous oxide was terminated. No signs of recurarization were noticed in any of the patients. In conclusion, this method of administration of ORG NC45 assures a stable level of curarization without side-effects. However, because of the different individual levels of sensitivity which were noted, this mode of administration requires careful monitoring to avoid inappropriate dosage.

Abdomen↗
PubMedDate not supplied

Effects of progressive muscle relaxation on blood pressure and psychosocial status for clients with essential hypertension in Taiwan.

This study examined the effect of progressive muscle relaxation (PMR) on blood pressure and psychosocial status in clients with essential hypertension. The study, which used a quasi-experimental design, recruited a convenience sample of 40 subjects from a hypertension outpatient clinic. Twenty subjects received PMR training once a week and practiced at home daily for 4 weeks. PMR training had an immediate effect, reducing pulse rate 2.35 beats/min, systolic blood pressure 5.44 mm Hg, and diastolic blood pressure 3.48 mm Hg. After 4 weeks of PMR training, further decreases in pulse rate (2.9 beats/min), systolic blood pressure (5.1 mm Hg), and diastolic blood pressure (3.1 mm Hg) occurred. PMR significantly lowered patients' perception of stress, and it enhanced their perception of health. PMR is beneficial for patients with essential hypertension, and nurses may use it to enhance their independent function as well as their quality of life.

Adult↗
PubMed1981

A double-blind comparative trial of new muscle relaxant, tizanidine (DS 103-282), and baclofen in the treatment of chronic spasticity in multiple sclerosis.

A double-blind trial with two parallel groups was carried out to compare the antispastic effect and tolerability of a new muscle relaxant, tizanidine (DS 103-282), with those of baclofen in the treatment of spasticity due to multiple sclerosis. Twenty-one hospitalized patients with stable spasticity participated in the 6-week trial. Eleven received tizanidine and 10 baclofen in gradually increasing daily doses. The optimal daily dose of tizanidine was between 8 and 36 mg and that of baclofen between 10 and 80 mg. Overall spastic state, spasms and clonus were similarly improved with both medications. In contrast, muscle strength, bladder function and the activities of daily living were more improved on tizanidine than on baclofen. Tiredness was the most frequent side-effect on tizanidine and muscle weakness on baclofen. The laboratory tests did not show any pathological changes with either medication. According to these results, tizanidine provides a new therapeutic alternative in the treatment of spasticity.

Adult↗
PubMed1981

Synthesis and skeletal muscle relaxant activity of 3-(aminoacyl)-1-[[[5-(substituted phenyl)-2-furanyl]methylene]amino] -2,4-imidazolidinediones.

A series of 3-(aminoacyl)-1-[[[5-(substituted phenyl)-2-furanyl] methylene]amino]-2,4-imidazolidinediones was synthesized and evaluated for skeletal muscle relaxant activity. All compounds were active by the intravenous route, and nine of 11 were active orally. One compound was very active when evaluated by the mouse Straub tail and rotarod tests; its efficacy index (ED50 rotarod/ED50 Straub tail) was 2.0, while its therapeutic index (LD50/ED50 Straub tail) was > 225.

Animals↗
PubMedDate not supplied

[Dynamics of muscle relaxation following unfused tetanus of different durations].

The isometric force of human m. flexor digitorum sublimis and its first time derivative were recorded during muscle relaxation. It was shown that after the prolonged unfused tetanus (phase iii) and in contractions in response to the repeated double pulses so called delayed relaxation with increase of TR/2 and typical "shoulder" on the relaxation curve can be observed. Delayed relaxation never can be seen in twitch. It was supposed that such type of relaxation is characteristic of the states of high activation of contractile machinery.

Biomechanical Phenomena↗
PubMed1999

Shortening of muscle relaxation time after creatine loading.

The effect of creatine (Cr) supplementation on muscle isometric torque generation and relaxation was investigated in healthy male volunteers. Maximal torque (Tmax), contraction time (CT) from 0.25 to 0.75 of Tmax, and relaxation time (RT) from 0.75 to 0.25 of Tmax were measured during 12 maximal isometric 3-s elbow flexions interspersed by 10-s rest intervals. Between the pretest and the posttest, subjects ingested Cr monohydrate (4 x 5 g/day; n = 8) or placebo (n = 8) for 5 days. Pretest Tmax, CT, and RT were similar in Cr and placebo groups. Also in the posttest, Tmax and CT were similar between groups. However, posttest RT was decreased consistently by approximately 20% (P < 0.05) in the Cr group from the first to the last of the 12 contractions. In addition, the mean decrease in RT after Cr loading was positively correlated with pretest RT (r = 0.82). It is concluded that Cr loading facilitates the rate of muscle relaxation during brief isometric muscle contractions without affecting torque production.

Adolescent↗
PubMed1999

Isoeugenolol: a selective beta1-adrenergic antagonist with tracheal and vascular smooth muscle relaxant properties.

Isoeugenolol (1.0, 3.0, 5.0 mg/kg, i.v.) produced a dose-dependent bradycardia and a decrease in blood pressure in anesthetized Wistar rats. Isoeugenolol inhibited the tachycardia effects induced by (-)isoproterenol, but had no blocking effect on the arterial pressor responses induced by (-)phenylephrine. In isolated guinea pig tissues, isoeugenolol antagonized (-)isoproterenol-induced positive inotropic and chronotropic effects on the atria and tracheal relaxations in a concentration-dependent manner. The apparent pA2 values for isoeugenolol on right atria, left atria and trachea were 7.63+/-0.03, 7.89+/-0.12 and 6.12+/-0.05, respectively, indicating that isoeugenolol was a highly selective beta1-adrenoceptor blocker. On the other hand, isoeugenolol produced a mild direct cardiac depression at high concentration and was without intrinsic sympathomimetic activity (ISA). In isolated rat thoracic aorta, isoeugenolol relaxed more potently the contractions induced by (-)phenylephrine (10 microM) and 5-HT (10 microM) than those by high K+ (75 mM). In isolated guinea pig trachea, isoeugenolol attenuated the carbachol (1 microM)-con-tracted trachea more significantly than those contracted with high K+. Furthermore, the binding characteristics of isoeugenolol and various beta-adrenoceptor antagonists were evaluated in [3H]CGP-12177 binding to rat ventricle, lung and interscapular brown adipose tissue (IBAT) membranes. The -log IC50 values of isoeugenolol for predominate beta1-, beta2- and beta3-adrenergic receptor sites were 5.82+/-0.09, 4.74+/-0.05 and 4.73+/-0.12, respectively. In conclusion, isoeugenolol was found to be a highly selective beta1-adrenoceptor antagonist with tracheal and vascular smooth muscle relaxant activities, but was devoid of alpha-adrenoceptor-blocking action.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1982

Selective depression of synaptic transmission of spinal neurones in the cat by a new centrally acting muscle relaxant, 5-chloro-4-(2-imidazolin-2-yl-amino)-2, 1, 3-benzothiodazole (DS103-282).

1 The effects of a new muscle relaxant, 5-chloro-(2-imidazolin-2-yl-amino)-2, 1, 3-benzothiodazole (DS103-282) have been examined on segmental reflexes and responses of single neurones in the spinal cord of the anaesthetized cat to stimulation of peripheral afferents, ventral roots, acetylcholine and various amino acids. Drugs were administered intravenously and/or iontophoretically.2 Polysynaptic reflexes were depressed in a dose-dependent manner by 0.01-0.1 mg/kg DS103-282 whereas monosynaptic reflexes were relatively insensitive to this agent.3 In studies on single dorsal horn neurones, iontophoretically and intravenously administered DS103-282 depressed synaptic excitatory responses, polysynaptic responses being much more sensitive to this agent than monosynaptic responses. In contrast (-)-baclofen preferentially reduced monosynaptic excitation.4 Doses or ejecting currents of DS103-282 which greatly depressed polysynaptic excitatory responses also reduced spontaneous firing of neurones, but either had no effect or minimal depressant effects on responses to iotophoretically administered excitant amino acids. Acetylcholine-induced excitation of Renshaw cells was depressed by iontophoretically (but not intravenously) administered DS103-282, although ventral root-evoked responses of these cells were insensitive to this agent.5 Inhibition of spinal neurones by stimulation of peripheral nerves or by iontophoresis of gamma-aminobutyric acid or glycine was unaffected by DS103-282.6 These results indicate that DS103-282 preferentially depresses peripherally evoked polysynaptic excitation of spinal neurones probably by an action on the terminals of excitatory interneurones.

Amino Acids↗
PubMed1997

Potency and kinetics of nitric oxide-mediated vascular smooth muscle relaxation determined with flash photolysis of ruthenium nitrosyl chlorides.

Flash photolysis of thermally stable, photolabile 'caged' precursors permits rapid and precise changes of ligand concentration at their site of action. This approach was used to determine the concentration-dependence and time course of NO-mediated relaxation of aortic smooth muscle, by use of two photolabile NO donors, trichloronitrosylruthenium (Ru(NO)Cl3) and dipotassium pentachloronitrosylruthenate (K2Ru(NO)Cl5). At concentrations up to 500 microM, both compounds were non-toxic before photolysis, and produced non-toxic by-products on photolysis. Photolytic release of NO produced relaxations of intact and endothelium-denuded aortic rings precontracted with noradrenaline (0.1-0.5 microM), with an EC50 for NO-mediated relaxations of 10.5 nM and 13 nM, respectively. NO-mediated relaxations were reversibly blocked by 1 microM oxyhaemoglobin. The time course of NO-mediated relaxation comprised a delay of 3-7 s, followed by a sigmoidal decline in tension with peak rates that were strongly dependent on NO concentration.

Acetylcholine↗
PubMed1990

Extension of the jaw opening reflex and effects of a central muscle relaxant (afloqualone) in the rat.

How widely the jaw opening reflex (JOR) extends was examined in the rat. Recording was done in the anterior (AD) and posterior (PD) digastric, sternohyoid (SH) and sternomastoid (SCM) muscles. Electric stimulation was given to the mandibular incisor pulp. Evoked electromyogram (EMG) activities could be recorded in each muscle. The thresholds for JOR increased from AD to SCM. Intravenously administered afloqualone, a centrally acting muscle relaxant, inhibited both JOR and its parallels promptly and dose-dependently. The possible clinical significance in temporomandibular joint dysfunction will be discussed.

Animals↗
PubMed1984

Studies on the muscle relaxation effects of ethyl loflazepate (CM6912) and evaluation as an anti-anxiety drug.

A new anti-anxiety drug, CM6912 (ethyl loflazepate, ethyl 7-chloro-2,3-dihydro-5-(2-fluorophenyl)-2-oxo-1H-1,4-benzodiazepine-3- carboxylate), was investigated for its effects on the alpha- and gamma-motor systems and on the cooperative muscular motions and for its interactions with other CNS drugs. The results obtained are as follows: Muscular discharges (EMG) induced by decerebrate rigidity were unaffected by 10 mg/kg (p.o.) of CM6912, but the amplitudes of the EMG were reduced by 50% for 3 hr by 30 mg/kg of CM6912 at 30 min after administration. Diazepam (10 mg/kg) also decreased the amplitudes of the EMG even at 5 min after administration, indicating that diazepam had a stronger than CM6912. Both monosynaptic spinal reflex (MSR) and polysynaptic spinal reflex (PSR) were unaffected by CM6912 (100 mg/kg). Dorsal root reflex potential was slightly enhanced by CM6912 (100 mg/kg), but not at a dose of 30 mg/kg. Diazepam (10 mg/kg) did not decrease MSR, but slightly reduced PSR. Dorsal root reflex potential was almost doubled by diazepam. The frequency of spontaneous discharges of Gla spindle afferent fiber of the extensor muscle of the hindlimb of anesthetized cats was unchanged by 10 mg/kg CM6912, but was suppressed by diazepam at the same dose while at a dose of 30 mg/kg, it was reduced mildly by CM6912, and markedly by diazepam. ED50 values for the antagonistic action on bemegride-induced convulsions were 0.30 mg/kg for CM6912 and 0.49 mg/kg for diazepam at 1 hr after administration, and they were 0.30 mg/kg and 0.67 mg/kg for CM6912 and diazepam, respectively, at 4 hr. The potentiating action of CM6912 on chlorprothixene-induced anesthesia was far weaker than that of diazepam. The suppressive potency of CM6912 on the adaptability to the rotarod was about half that of diazepam, and the muscle relaxant action of CM6912, examined by the inclined board test and the hanging test, was found to be similar to that of diazepam. These results suggest that CM6912 is less potent than diazepam in reducing muscular tone and in inducing sleep, while it has a stronger and longer-lasting anti-anxietic activity than diazepam.

Adaptation, Psychological↗
PubMed1999

Inhibition of the ATP-dependent interaction of actin and myosin by the catalytic domain of the myosin light chain kinase of smooth muscle: possible involvement in smooth muscle relaxation.

Myosin light chain kinase (MLCK) phosphorylates the light chain of smooth muscle myosin enabling its interaction with actin. This interaction initiates smooth muscle contraction. MLCK has another role that is not attributable to its phosphorylating activity, i.e., it inhibits the ATP-dependent movement of actin filaments on a glass surface coated with phosphorylated myosin. To analyze the inhibitory effect of MLCK, the catalytic domain of MLCK was obtained with or without the regulatory sequence adjacent to the C-terminal of the domain, and the inhibitory effect of the domain was examined by the movement of actin filaments. All the domains work so as to inhibit actin filament movement whether or not the regulatory sequence is included. When the domain includes the regulatory sequence, calmodulin in the presence of calcium abolishes the inhibition. Since the phosphorylation reaction is not involved in regulating the movement by MLCK, and a catalytic fragment that shows no kinase activity also inhibits movement, the kinase activity is not related to inhibition. Higher concentrations of MLCK inhibit the binding of actin filaments to myosin-coated surfaces as well as their movement. We discuss the dual roles of the domain, the phosphorylation of myosin that allows myosin to cross-bridge with actin and a novel function that breaks cross-bridging.

Actins↗