Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In addition to producing antinociception and mild sedation, opiates diminish spontaneous movement and produce muscle rigidity. Examination of the relationship between different opiate effects may lead to a better understanding of the mechanism and sites of action of opiate anesthesia. Previous studies have compared the dose-effect relationships for morphine and fentanyl between antinociception and loss of righting reflex. However, neither muscle rigidity nor lack of spontaneous movement (as measured by catalepsy) has been fully examined or directly compared with either antinociception or loss of righting reflex. This study, therefore, compared five clinically relevant opiate endpoints (antinociception, muscle rigidity, catalepsy, loss of righting reflex, and respiratory depression) using the mu-selective agonist alfentanil in the spontaneously ventilating rat. Rats were randomized to receive alfentanil (0-500 micrograms/kg) subcutaneously. For muscle rigidity, 59 rats had electromyographic activity measured with percutaneous hindlimb electrodes. After alfentanil injection, electromyographic data were recorded for 60 min. For antinociception and catalepsy, 49 rats were studied for 120 min after alfentanil. Catalepsy was measured from the time the rat's forelimbs were placed on a 10-cm-high bar until either limb was removed. Antinociception was studied by measuring tail-flick response to hot (55 degrees C) water. For righting reflex, 40 rats were studied for 120 min. Alfentanil-induced respiratory depression was assessed in 40 rats with indwelling tail arterial catheters. Alfentanil was administered after baseline arterial blood gas measurements, and then additional samples were obtained for 45 min. For each effect, data were converted into quantal responses and were then transformed to probit-log dose-response curves for analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elucidation of dose-effect relationships for different opiate effects using alfentanil in the spontaneously ventilating rat. 160 89

The experiments examined the characteristics of analgesia produced by different doses of morphine, meperidine (pethidine), fentanyl, and sufentanil after epidural and subcutaneous injection in rats. The specificity of the analgesia was also determined; other in vivo pharmacologic activities (i.e., blockade of pinna and cornea reflexes and production of skeletal muscle rigidity) were monitored as pharmacologic indices of opiate drug activity in the brain. After subcutaneous injection, the opiates produced dose-dependent analgesia, blocked the pinna and cornea reflexes, and induced muscle rigidity. After epidural injection, all four compounds produced dose-dependent analgesia and had greater potency, earlier onset, shorter duration, and greater specificity of analgesic action than was the case after subcutaneous injection. Specificity is defined here as the ratio of the ED50 dose that blocked the pinna reflex to the ED50 dose that produced analgesia. The gains in potency and specificity, but not the gains in onset time and the losses in duration of analgesia, differed considerably among the compounds that were examined. The subcutaneous-to-epidural potency ratio related in a linear manner with the lipid-to-water partition coefficient. The gain in specificity also appeared to be related to lipid solubility. The microgram X kg-1 doses at which the opiates produced analgesia in rats correlate well with the potency of these compounds in producing analgesia after epidural injection in humans. The rat epidural preparation reflected the doses, onset, and specificity, but not the duration, of analgesia produced by epidural opiates in humans.
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PMID:Epidural and subcutaneous morphine, meperidine (pethidine), fentanyl and sufentanil in the rat: analgesia and other in vivo pharmacologic effects. 294 76

Previous studies in isolated limbs using crystalloid perfusion solutions have shown that control of the initial reperfusion reduces postischaemic complications. However, no experimental study has been undertaken to evaluate the concept of controlled limb reperfusion experimentally in an in vivo blood-perfused model and to assess the local as well as systemic effects of normal blood reperfusion and controlled limb reperfusion. Of 20 pigs undergoing preparation of the infrarenal aorta and iliac arteries, six were observed for 7.5 h and served as controls; 14 others underwent 6 h of complete infrarenal occlusion. Thereafter, embolectomy was simulated in eight pigs by removing the aortic clamp and establishing normal blood reperfusion at systemic pressure. In six other pigs, the composition of the reperfusate and the conditions of reperfusion were controlled during the first 30 min, followed by normal blood reperfusion. Some 6 h of infrarenal aortic occlusion leads to a severe decrease in high-energy phosphates and muscle temperature, together with a slight increase in creatine kinase and potassium in the systemic circulation. Normal blood reperfusion resulted in severe reperfusion injury: massive oedema developed, the tissue showed a marked decrease in oxygen consumption, glucose consumption, tissue ATP, total adenine nucleotides, muscle pH and total calcium in the femoral vein. Furthermore, a massive increase was seen in plasma creatine kinase concentration and potassium, together with the development of muscle rigidity. In sharp contrast, initial treatment of the ischaemic skeletal muscle by controlled limb reperfusion resulted in normal water content, oxygen consumption, glucose consumption, flow and muscle rigidity. Furthermore, controlled limb reperfusion resulted in higher total adenine nucleotides content, less tissue acidosis, markedly reduced creatine kinase release, and potassium release as compared with that of normal blood reperfusion. This study shows that 6 h of acute infrarenal aortic occlusion will result in severe reperfusion injury (postischaemic syndrome) if normal blood at systemic pressure is given in the initial reperfusion phase. In contrast, initial treatment of the ischaemic skeletal muscle by controlled limb reperfusion reduces the metabolic, functional and biochemical alterations.
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PMID:Reperfusion injury in skeletal muscle: controlled limb reperfusion reduces local and systemic complications after prolonged ischaemia. 785 92

Alfentanil is a potent and short-acting mu opioid agonist that produces both antinociceptive effects and muscle rigidity. In the present study, the susceptibility of alfentanil-induced antinociception and rigidity to antagonism by the selective mu antagonist beta-funaltrexamine and the selective mu-1 antagonist naloxonazine was examined. Alfentanil (37.7-150.0 micrograms/kg) produced a dose-dependent increase both in antinociception as measured by the warm-water tail-dip assay and in rigidity as measured by electromyographic recording of the gastrocnemius muscle. Both beta-funaltrexamine (10.0 and 20.0 mg/kg) and naloxonazine (7.5 and 15.0 mg/kg) produced dose-dependent and parallel rightward shifts in the alfentanil dose-effect curves for both antinociception and rigidity. Furthermore, the alfentanil dose-effect curves for antinociception and rigidity were shifted to the right to a similar degree by any given pretreatment. These results suggest that alfentanil-induced antinociception in the warm-water tail-dip test and rigidity are mediated by pharmacologically similar populations of opioid receptors. More specifically, these results suggest that mu-1 opioid receptors mediate both alfentanil-induced antinociception and rigidity.
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PMID:Antagonist effects of beta-funaltrexamine and naloxonazine on alfentanil-induced antinociception and muscle rigidity in the rat. 843 22

Our previous studies in isolated rat hindlimbs using crystalloid perfusion solutions have shown that control of the initial reperfusion reduces postischemic complications. However, no experimental study has been undertaken to evaluate the concept of controlled limb reperfusion experimentally in an in-vivo blood-perfused model and to assess the local as well as systemic effects of normal blood reperfusion and controlled limb reperfusion. Of twenty pigs undergoing preparation of the infrarenal aorta and iliac arteries, six were observed for 7.5 hours and served as controls. Fourteen other pigs underwent 6 hours of complete infrarenal occlusion. Thereafter, embolectomy was stimulated in 8 pigs by removing the aortic clamp and establishing normal blood reperfusion at systemic pressure. In 6 other pigs, control of the composition of the reperfusate and control of the conditions of reperfusion was done during the first 30 min, followed by normal blood reperfusion. Six hours of infrarenal aortic occlusion lead to a severe decrease in high energy phosphates and muscle temperature and a slight increase in creating kinase (CK) and potassium in the systemic circulation. Normal blood reperfusion resulted in severe reperfusion injury: massive edema developed (80.6% vs. 76.6%, p < 0.0009), the tissue showed a marked decrease in oxygen consumption (7.3 +/- 1.1 vs. 14.3 +/- 2.5 mL )2/100 g/min, p < 0.02), glucose consumption (0.19 +/- 0.06 vs. 0.51 +/- 0.03 mg/100 g/min, p < 0.06), tissue ATP (18.3 +/- 1.9 vs. 36.1 +/- 0.9 mumol/g protein, p < 0.000001), total adenine nucleotides (26.3 +/- 2.6 vs. 45.8 +/- 1.5 mumol/g protein, p < 0.00001), muscle pH (5.9 +/- 0.1 vs. 7.3 +/- 0.1, p < 0.000006) and total calcium in the femoral vein (2. +/- 0.1 vs. 2.7 +/- 0.1 mmol/L, p < 0.002). Furthermore, a massive increase was seen in CK concentration (12,743 +/- 2,562 vs. 513 +/- 80 U/L, p < 0.0003), potassium (7.9 +/- 0.3 vs. 4.4 +/- 0.2 mmol/L, p < 0.000001) and muscle rigidity (60 +/- 11 vs. 122 +/- 1 degree, p < 0.00008). In sharp contrast, initial treatment of the ischemic skeletal muscle by controlled limb reperfusion resulted in normal water content (77.6 +/- 0.4 vs. 76.8 +/- 0.3%), oxygen consumption (13.2 +/- 1.6 vs. 14.9 +/- 3.2 mL O2/100 g/min), glucose consumption (0.58 +/- 0.18 vs. 0.46 +/- 0.11 mg/100 g/min), flow (5.4 +/- 1.1 vs. 4.6 +/- 4.6 +/- 0.5 mL/100 g/min) and muscle rigidity (106 +/- 4 vs. 122 +/- 1 degree). Furthermore, controlled limb reperfusion resulted in higher total adenine nucleotides content (78% vs. 57% of control), less tissue acidosis (6.6 +/- 0.2 vs. 5.9 +/- 0.1, p < 0.002), severely reduced CK release (2,618 +/- 702 vs. 12,743 +/- 2.562, p < 0.02) and potassium release (5.1 +/- 0.3 vs. 7.9 +/- 0.3 mmol/L, p < 0.0002) as compared to normal blood reperfusion. In conclusion this study shows that 6 hours of acute infrarenal aortic occlusion will result in a severe reperfusion injury (postischemic syndrome) if normal blood at systemic pressure is given in the initial reperfusion phase. In contrast, initial treatment of the ischemic skeletal muscle by controlled limb reperfusion reduces the metabolic, functional and biochemical alterations.
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PMID:[Controlled reperfusion of the extremities for preventing local and systemic damage after prolonged ischemia. An experimental study with the swine model]. 901 38

The traditional view of opioids held that the individual opioid agonists shared the same mechanism of action, differing only in their potency and pharmacokinetic properties. However, recent advances in opioid receptor pharmacology have made this view obsolete. Distinguishing features of the synthetic opioid agonists are related, at least in part, to variation in affinity and intrinsic efficacy at multiple opioid receptors. Respiratory depression is the opioid adverse effect most feared by anaesthesiologists. Specific kappa-receptor agonists produce analgesia with little or no respiratory depression. There are a number of commercially available kappa-receptor partial agonist drugs, the so-called agonist-antagonist or nalorphine-like opioids, which appear to have a limited effect on breathing. Within the series of fentanyl analogues there are differences in behaviour towards particular opioid receptors and there is evidence for subtle differences in respiratory depressant effects. Pethidine (meperidine) causes histamine release and myocardial depression, while the fentanyl analogues do not. Pethidine has atropine-like effects on heart rate, while fentanyl analogues reduce heart rate by a vagomimetic action. Severe bradycardia or even asystole is possible with fentanyl analogues, especially in conjunction with the vagal stimulating effects of laryngoscopy. Fentanyl analogues often produce minor reductions in blood pressure, and occasionally severe hypotension by centrally mediated reduction in systemic vascular resistance. Muscle rigidity and myoclonic movement occurs frequently during induction of anaesthesia with larger doses of opioids. Fentanyl and alfentanil have been reported to produce localised temporal lobe electrical seizure activity in patients with complex partial epilepsy. There are probably fewer biliary effects with agonist-antagonist opioids than the agonist opioids. The mechanism of adverse effects after spinal administration is distinctly different for morphine, which is very water soluble, compared with more lipid-soluble opioids. The systemic absorption of morphine after intrathecal or epidural administration is very slow, resulting in long duration of analgesia and low plasma concentrations, while lipid-soluble opioids are rapidly absorbed into the circulation and redistributed to the brain. The serotonin syndrome may result from coadministration of pethidine, dextromethorphan, pentazocine or tramadol with monoamine oxidase inhibitors (MAOIs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). There are clinically important interactions between opioids and hypnosedatives, resulting in synergistic effects on sedation, breathing and blood pressure.
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PMID:Adverse effects of opioid agonists and agonist-antagonists in anaesthesia. 974 65

The turkey industry suffers from pale, soft, and exudative meat (PSE) that is unsuitable for further processing because of excessive color variation, poor meat binding, and depressed water holding ability. This condition is caused by accelerated postmortem muscle metabolism and is thought to be related to a similarly inherited condition in swine. A quick, nondestructive method of screening animals is needed to avoid further propagation of PSE in breeding flocks. In this study, a halothane test used with swine was evaluated as a possible detection method for PSE-susceptible turkeys. In Experiment 1, a commercial strain of 4-wk-old male turkeys (n = 116) was exposed to 3% halothane gas for 3 min (6 L/min) and examined for leg muscle rigidity. Experiment 2 followed similar testing measures, using two strains of growth-selected turkeys (n = 504). Measurements of pH, R-value (ratio of inosine:adenosine), color, and expressible moisture content were made from each bird's breast fillet to determine whether the muscles of the responding birds would develop PSE characteristics. Five percent of tested birds in the first experiment and 2% in the second experiment exhibited rigid legs, indicating some of the discriminating power of this test. However, the data indicated that the characteristics of muscles from these birds did not differ from those of the nonresponding birds (P < 0.05). Possibly, the birds may need to be screened or slaughtered at a different age or using different methods.
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PMID:A halothane test to detect turkeys prone to developing pale, soft, and exudative meat. 1056 Aug 40

Rigidity is one of the oldest psychological constructs, with systematic research dating back to the late 19th century. The authors review this research in an attempt to clarify the construct of rigidity and to investigate its correlates. Rigidity is described as a multidimensional construct encompassing the tendency to form and perseverate in the use of mental and behavioral sets. A series of meta-analyses was performed based on three measures of behavioral rigidity: the Einstellung Water-Jar Task, the Wisconsin Card Sorting Task, and the motor-cognitive dimension of the Test of Behavioral Rigidity. The results indicated that rigidity is curvilinearly related to age, positively related to authoritarianism (particularly under stressful situations), and negatively related to intelligence; that men are more rigid than women; that obsessive-compulsiveness is positively related to rigidity; and that schizophrenics are more rigid than nonschizophrenic siblings and normal controls. Unresolved issues and gaps in the research are discussed.
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PMID:Rigidity of thought and behavior: 100 years of research. 1219 21

A case of fatal suicidal bentazon poisoning is presented along with a description of the different analytical methods involved. A 56-year-old farmer was examined by the family doctor 1 h after voluntarily ingesting 500 mL of FIGHTER (bentazon, 480 g/L water). He presented a Glasgow score of 15, polypnea, diarrhea, and vomiting. During transport by ambulance to the hospital, he tossed, sweated, and suddenly presented breathing difficulty followed by heart failure. Tracheal intubation was impossible (H1.5) despite use of different diameter cannulas because of extreme general muscle rigidity. All attempts at resuscitation failed, and the patient died within 2 h postingestion. Blood and urine samples were taken just before death. General basic and neutral drug screening by high-performance liquid chromatography-diode-array detection and gas chromatography-nitrogen-phosphorus detection showed no strychnine or other drugs or toxics except for citalopram (< 0.1 mg/L) and bentazon, but this weak acidic molecule (pKa3.3) was badly extracted in alkaline conditions. Plasma and urine levels, measured after acidic extraction, protein precipitation, or simple dilution, were 1500 and 1000 mg/L, respectively. Bentazon (M.W. 240) was confirmed by its basic mass spectrum (ESI-, m/z 239, 197, 175, 132) or by that of methylated derivative (El+, m/z 254, 212, 175). An hydroxylated metabolite (ESI-, m/z 255, 213, 191, 148; El+, m/z 284, 242, 163) and the N1-glucuronide conjugate of bentazon (ESI-, m/z 415, 239) were also detected in urine. (Quantitation ions are underlined.) This first case of bentazon poisoning with available analytical data revealed the high toxicity of this compound after large dose ingestion with early and heavy symptoms such as muscle rigidity probably related to muscular toxicity. Comparison with another nonfatal case and with toxicological data on animals is discussed.
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PMID:Fatal acute poisoning by bentazon. 1267 7

Within the last several years, the poultry industry has seen a dramatic increase in the occurrence of pale, soft, and exudative (PSE) meat. This problem is known to be associated with a rapid decline in postmortem (PM) muscle pH, which results in inferior protein functionality similar to that found in PSE pork. Many factors such as seasonal changes have been known to influence the occurrence of PSE meat in poultry and swine. Halothane and succinylcholine have been used within the pork industry to identify animals susceptible to stress and prone to developing PSE meat. The mechanism for the triggering of the PSE gene in poultry has not been fully understood. Therefore, a study was conducted to determine the effectiveness of screening broilers with halothane to identify those prone to developing PSE meat. Succinylcholine was used before slaughter to serve as a triggering agent for the PSE condition. At 4 wk of age, broilers from 4 commercial strains (n = 1,000) were subjected to 3% halothane gas and classified as either halothane positive (HAL+) or negative (HAL-) based on muscle rigidity within the legs. Although halothane sensitivity varied slightly among the strains, approximately 14% of the birds overall were classified as HAL+. All HAL- birds (n = 163) and an equal number of HAL-birds (n = 163) in each strain were grown to market age (7 wk) and were commercially processed. At the time of processing, half of the HAL+ and HAL- birds were injected intravenously with succinylcholine and were slaughtered at 0.25 h postinjection. Pectoralis muscle samples were collected at 0.25, 2, 5, and 24 h PM for the evaluation of rigor development (muscle pH) and meat quality (L* value, moisture, drip loss, and cook loss). Halothane sensitivity had no effect on rigor development, muscle color, or water-holding capacity in the 4 broiler strains. Although birds exhibited reactions to the halothane gas, the halothane sensitivity, along with the use of succinylcholine, was not able to identify birds prone to developing PSE meat.
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PMID:The use of halothane and succinylcholine to identify broilers prone to developing pale, soft, exudative meat. 1533 22


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