naloxone and Muscle-Rigidity

Food and Drug Administration (FDA) risk evaluation and mitigation strategies (REMs) encourage emergency responders, paramedics, law enforcement agents, and even laypeople to be trained in the administration of naloxone with the intent of rescuing individuals from a known or suspected opioid overdose.. Although naloxone is generally safe and effective at reversing respiratory depression caused by a conventional opioid such as morphine or heroin by competing with the opioid and displacing it from the μ-opioid receptor, questions increasingly are arising as to whether naloxone can adequately reverse opioid overdoses that may involve the potent opioids fentanyl and its analogues (F/FAs). In other words, as more and more opioid overdoses involve F/FAs, can naloxone keep up?. As a competitive antagonist at μ-opioid receptors, naloxone is often a life-saving agent in cases of overdose caused by conventional opioids, but it may not be versatile or powerful enough to combat the rising tide of overdoses due to fentanyl and its illicit analogues, or in cases of overdose involving combinations of opioids and non-opioids.

Topics: Diaphragm; Dose-Response Relationship, Drug; Fentanyl; Heroin; Humans; Laryngismus; Muscle Rigidity; Naloxone; Narcotic Antagonists; Opiate Overdose; Receptors, Opioid, mu; Thoracic Wall

Topics: Adrenergic Neurons; Analgesics, Opioid; Drug Overdose; Fentanyl; Humans; Muscle Rigidity; Naloxone; Narcotic Antagonists; Opioid Epidemic; Respiratory Insufficiency; Time-to-Treatment

A 22.5-kg, 8.4-year-old female mixed breed dog was presented for an emergency ovariohysterectomy for pyometra. No neurological abnormalities were observed on preoperative physical examination. Surgery was completed uneventfully under fentanyl- and sevoflurane-based anaesthesia. Cardiorespiratory indices remained stable under mechanical ventilation throughout the procedure. Approximately 23 min after the discontinuation of fentanyl infusion, the investigator noticed jaw closure and stiffness and thoraco-abdominal muscle rigidity. To rule out fentanyl-induced muscle rigidity, naloxone was administered. Following administration of naloxone, there was a return of spontaneous respiratory effort, indicated by capnogram and visible chest wall excursion. Based on the clinical signs and response to naloxone administration, the dog was diagnosed with suspected fentanyl-induced muscle rigidity. Six minutes after the return of spontaneous respiration, the dog was extubated uneventfully without additional naloxone administration. During 4 days of postoperative hospitalization, no recurrent muscle rigidity was observed, and the patient was discharged safely. The total dose of fentanyl administered was 0.61 mg (27 μg kg

Topics: Abdominal Muscles; Analgesics, Opioid; Animals; Dog Diseases; Dogs; Female; Fentanyl; Muscle Rigidity; Naloxone; Respiration, Artificial

In a constantly increasing world of opioid addiction, naloxone has become a topic of great discussion and use. With seemingly minimal side effects, naloxone has become one of the most wellknown and widely used reversal agents for opioid intoxication. While more common effects of using naloxone include agitation, abdominal cramps, piloerection, diarrhea, nausea, and yawning, lesser known side effects involve muscle spasms, flushing, hyperreflexia in neonates, and seizures. This case study demonstrates a side effect of rigidity secondary to IV naloxone that has not previously been documented.. A 56 year old man was brought in by EMS after being found unresponsive in a car with a bag of drugs beside him. He was given 0.5 mg naloxone IV by EMS and immediately brought to the hospital. On arrival, the pt was noted to have tight rigidity of his upper extremities, with severe flexion. This presentation was not noted before the delivery of naloxone by EMS.. While this case highlights a patient with a rare side effect of naloxone, it reminds physicians that all medications come with a cost. Of course, ABCs remain the highest priority of resuscitation, however when administering a medication to reverse a drug overdose, it is important to keep in mind all possible consequences of said agent. Recognizing that complete muscle rigidity may remain a result of naloxone administration allows physicians to perhaps save patients from further medical workup.

Topics: Adult; Analgesics, Opioid; Emergency Service, Hospital; Female; Humans; Muscle Rigidity; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Syndrome; Thoracic Wall

Topics: Drug Overdose; Fentanyl; Humans; Muscle Rigidity; Naloxone; Narcotic Antagonists; Narcotics; Receptors, Opioid, mu; Respiratory Insufficiency; Respiratory Muscles

Topics: Analgesics, Opioid; Female; Fentanyl; Humans; Middle Aged; Muscle Rigidity; Naloxone; Narcotic Antagonists; Respiration, Artificial; Respiratory Muscles; Risk Factors; Thoracic Wall

Fentanyl and other opiates used in procedural sedation and analgesia are associated with several well-known complications. We report the case of a man who developed the uncommon complication of chest wall rigidity and ineffective spontaneous ventilation following the administration of fentanyl during an elective bronchoscopy. His ventilation was assisted and the condition was reversed with naloxone. Although this complication is better described in pediatric patients and with anesthetic doses, chest wall rigidity can occur with analgesic doses of fentanyl and related compounds. Management includes ventilatory support and reversal with either naloxone or a short-acting neuromuscular blocking agent. This reaction does not appear to be a contraindication to future use of fentanyl or related compounds. Chest wall rigidity causing respiratory compromise should be readily recognized and treated by bronchoscopists.

Topics: Aged; Analgesics, Opioid; Bronchoscopy; Fentanyl; Humans; Male; Muscle Rigidity; Naloxone; Narcotic Antagonists; Thoracic Wall; Treatment Outcome

Since its introduction into clinical practice, it has been known that fentanyl and other synthetic opioids may cause skeletal muscle rigidity. Involvement of the respiratory musculature, laryngeal structures, or the chest wall may impair ventilation, resulting in hypercarbia and hypoxemia. Although most common with the rapid administration of large doses, this rare adverse effect may occur with small doses especially in neonates and infants. We present 2 infants who developed chest wall rigidity, requiring the administration of neuromuscular blocking agents and controlled ventilation after analgesic doses of fentanyl. Previous reports regarding chest wall rigidity after the administration of low-dose fentanyl in infants and children are reviewed, the pathogenesis of the disorder is discussed, and treatment options offered.

Topics: Analgesics, Opioid; Dose-Response Relationship, Drug; Female; Fentanyl; Follow-Up Studies; Humans; Hypercapnia; Infant; Infant, Newborn; Injections, Intravenous; Muscle Rigidity; Naloxone; Narcotic Antagonists; Thoracic Wall

The inability to appropriately ventilate neonates shortly after their birth could be related in rare cases to chest-wall rigidity caused by the placental transfer of fentanyl. Although this adverse effect is recognized when fentanyl is administered to neonates after their birth, the prenatal phenomenon is less known. Treatment with either naloxone or muscle relaxants reverses the fentanyl effect and may prevent unnecessary excessive ventilatory settings.

Topics: Cesarean Section; Female; Fentanyl; Humans; Infant, Newborn; Infant, Premature, Diseases; Muscle Rigidity; Naloxone; Narcotic Antagonists; Narcotics; Pregnancy; Pregnancy Complications, Infectious; Pyelonephritis; Respiratory Distress Syndrome; Thoracic Wall

To describe a potentially fatal adverse drug event after administration of morphine to a term neonate.. A 2-day-old term neonate experienced generalized muscle rigidity and laryngeal spasm resulting in acute respiratory failure on 2 separate occasions after morphine administration. The first occasion was after administration of bolus doses of fentanyl and morphine 100 microg/kg in the operating theater; administration of intravenous propofol 2 mg/kg resulted in relief of muscle rigidity. The second occasion occurred a few hours later, when the patient received a continuous infusion of morphine 4.4 microg/kg/h in the intensive care unit and experienced generalized muscle rigidity with respiratory compromise. The opioid antagonist naloxone 30 microg/kg was administered intravenously, which immediately resulted in a patent airway and spontaneous breathing. An objective causality assessment using the Naranjo probability scale revealed that the likelihood of morphine causing the patient's muscle rigidity on the second occasion was highly probable to definite. It is not clear whether the first occurrence of muscle rigidity was morphine-induced.. We searched PubMed and EMBASE (through August 2009) for previous reports of morphine-related muscle rigidity and/or laryngeal spasm, using the search terms (muscle rigidity OR chest rigidity OR laryngeal spasm) AND (morphine OR fentanyl OR opioid). Sudden onset of muscle rigidity and laryngeal spasm is described in the literature as a rare but serious adverse event after infusion of fentanyl and similar opioids in both adults and young infants. However, there are no reports of this potentially fatal adverse event after administration of morphine. To our knowledge this is the first case reported of life-threatening muscle rigidity and laryngeal spasm after therapeutic doses of morphine in humans.. A serious adverse event consisting of generalized muscle rigidity and laryngospasm can occur after bolus administration of morphine as well as during continuous infusion. Clinicians should be aware of this possibility.

Topics: Analgesics, Opioid; Fentanyl; Humans; Infant, Newborn; Male; Morphine; Muscle Rigidity; Naloxone; Narcotic Antagonists; Propofol

To evaluate the utility and safety of remifentanil for hemodynamic control during cesarean section in high-risk patients ineligible for spinal anesthesia.. One minute before induction we injected a bolus of 1 microg x kg(-1) of remifentanil, followed by propofol (2.5 mg x kg(-1)), succinylcholine (1 mg x kg(-1)), cisatracurium, sevoflurane in oxygen and nitrous oxide, and fentanyl (5 microg x kg(-1)) after clamping the umbilical cord. We recorded maternal hemodynamic variables, pulse oximetry, capnography, bispectral index, and presence of muscular rigidity. In the neonate we assessed fetal wellbeing, weight, and requirement for naloxone. Hemodynamic stability was defined as no more than 15% variation in arterial pressure with respect to baseline.. Twelve patients undergoing surgery because of placenta abruptio, subarachnoid hemorrhage, HELLP syndrome, or preeclampsia were enrolled. Hemodynamic variables were consistently stable during surgery in all patients. No cases of neonatal rigidity were noted and there was no need for naloxone. The mean Apgar score was 6.42 (1.5) at 1 minute and 8.42 (0.9) at 5 minutes.. Bolus injection of 1 microg x kg(-1) of remifentanil may be useful for maintaining maternal hemodynamic stability in high-risk obstetric cases. Given the risk of neonatal depression, this resource should be used selectively and the means for neonatal resuscitation should be available.

Topics: Adult; Anesthetics, Intravenous; Atracurium; Cesarean Section; Female; Fentanyl; Fetus; Hemodynamics; Humans; Infant, Newborn; Methyl Ethers; Muscle Rigidity; Naloxone; Nitrous Oxide; Piperidines; Pregnancy; Pregnancy Complications; Pregnancy, High-Risk; Propofol; Remifentanil; Resuscitation; Retrospective Studies; Sevoflurane; Succinylcholine

To present and discuss a case of opioid-induced rigidity with low-dose fentanyl during recovery from anesthesia.. A 41-yr-old woman underwent laparotomy for total abdominal hysterectomy and bilateral salpingo- oophorectomy under general anesthesia. She received a total of 500 micro g of fentanyl by iv intermittent boluses during the three-hour anesthetic. During emergence from anesthesia, while intubated, the patient presented with rigidity. No changes in ventilatory parameters were measured during the episode. The only notable predisposing factor was treatment with venlafexine, an antidepressant that modifies serotonin and norepinephrine levels. She was successfully treated with iv naloxone 20 micro g. The rest of the postoperative period was uneventful.. We observed an atypical case of opioid-induced rigidity in contrast to the classical syndrome, which presents at induction with high-dose opioids. This syndrome has many clinical presentations with neurologic and ventilatory signs of varying intensity. Early recognition of the syndrome and adequate treatment is crucial. If treated adequately, opioid-induced rigidity is self-limited with few complications.

Topics: Adult; Analgesics, Opioid; Anesthesia Recovery Period; Anesthesia, General; Antidepressive Agents, Second-Generation; Cyclohexanols; Drug Synergism; Female; Fentanyl; Humans; Muscle Rigidity; Naloxone; Narcotic Antagonists; Venlafaxine Hydrochloride

A number of potential neurochemical mediators of opiate-induced muscle rigidity have been proposed based on the results of systemic drug studies and on knowledge of the brain sites implicated in opiate rigidity. The effects of i.c.v. pretreatment with selected opioidergic, alpha adrenergic and serotonergic drugs on muscle rigidity induced with systemic injection of the potent opiate agonist alfentanil (ALF) were investigated in spontaneously ventilating rats. The opiate antagonist methylnaloxonium (MN; 0.2-14 nmol), alpha-2 adrenergic agonists dexmedetomidine (DEX; 0.4-42 nmol) or 2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride (ST91; 4-400 nmol), alpha-1 adrenergic antagonist prazosin (PRZ; 7-70 nmol) or serotonergic antagonist ketanserin (KET; 18-550 nmol) were injected i.c.v. (10 microliters) and ALF (500 micrograms/kg s.c.) was administered 10 min later. S.c. electrodes were used to record gastrocnemius electromyographic activity. Both MN and DEX dose-dependently and potently antagonized ALF-induced rigidity. ST91 produced shorter-lived, less profound, antagonism of ALF rigidity. PRZ, at the highest dose tested, produced a delayed and modest reduction in ALF rigidity. A large, non-selective, dose of KET incompletely attenuated ALF rigidity. These results lend support to the hypothesis that central opioid and alpha-2 adrenergic receptors mediate opiate-induced muscle rigidity in the rat.

Topics: Adrenergic alpha-Agonists; Alfentanil; Animals; Electromyography; Hindlimb; Imidazoles; Ketanserin; Male; Medetomidine; Muscle Rigidity; Naloxone; Narcotics; Quaternary Ammonium Compounds; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-2

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.

Topics: Alfentanil; Analgesia; Animals; Electromyography; Male; Muscle Rigidity; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Rats, Wistar

A dilute solution of formalin (20 microliters of 10% formalin) was injected subcutaneously in the dorsal right hind paw of the naked mole-rat. The injection of the dilute formalin produced two periods of pain behaviour, the early (0-5 minutes) and the late phase (25-60 minutes). These were quantified as the total time spent licking the injected paw. Codeine phosphate (10, 25 or 50 mg kg-1) significantly reduced pain behaviour in both the early and late phase. Codeine administration also induced aggressive, hyperactive behaviour and motor impairment that was naloxone (2 mg kg-1) reversible. Naproxen (200 mg kg-1) and dexamethasone phosphate (30 mg kg-1) significantly reduced licking activity in the late phase only.

Topics: Animals; Behavior, Animal; Codeine; Dexamethasone; Dose-Response Relationship, Drug; Formaldehyde; Injections, Intraperitoneal; Injections, Subcutaneous; Muscle Rigidity; Naloxone; Naproxen; Pain; Rodentia

Previous work has demonstrated that direct injections of methylnaloxonium (MN), a hydrophilic quaternary opiate antagonist, in the area of the nucleus raphe pontis (RPn) significantly attenuated alfentanil-induced muscle rigidity in the rat. To extend these observations and to explore further the regions important for opiate-induced rigidity, rats were implanted with chronic guide cannulae aimed at discrete brain sites with an emphasis on the region from the periaqueductal grey (PAG) to the RPn. Each animal was pretreated by a blinded observer with an intracerebral injection of MN (125 ng total dose) or saline, and electromyographic (EMG) activity was recorded from the gastrocnemius muscle. Alfentanil (ALF; 500 micrograms/kg) was then administered subcutaneously and the magnitude of tonic EMG activity was assessed as a measure of hindlimb rigidity. The administration of MN into the pontine raphe nucleus (RPn) and also into the more lateral nucleus reticularis tegmenti pontis significantly attenuated ALF rigidity compared with saline-pretreated controls. Within the midbrain, MN selectively reversed rigidity when injected into the periaqueductal grey (PAG). The dorsal PAG appeared to be a more important site than the ventral PAG. There was no significant effect on ALF rigidity of MN injections into brain regions between the ventral PAG and the RPn while MN injections into the deep layers of the superior colliculus, lateral to the dorsal PAG, partially attenuated ALF rigidity. In contrast, rigidity was not consistently reversed after MN injections into the basal ganglia, the dorsal superior colliculus, or the region of the decussation of the dorsal tegmentum. This study provides strong evidence that nuclei of the reticular formation, specifically the PAG, raphe pontis, and reticularis tegmenti pontis that are known to play a role in other opioid-mediated behaviors, are important in opiate-induced muscle rigidity in the rat. These results could have implications for the prevention of this undesirable effect of high-dose opiate administration.

Topics: Alfentanil; Animals; Electromyography; Hindlimb; Injections; Muscle Rigidity; Naloxone; Narcotics; Periaqueductal Gray; Quaternary Ammonium Compounds; Raphe Nuclei; Rats; Rats, Inbred Strains

Previous work has demonstrated that direct injections of methylnaloxonium (MN), a relatively lipophobic quaternary opiate antagonist, in the area of the nucleus raphe pontis (RPn) significantly attenuated alfentanil-induced rigidity. It was hypothesized that other hindbrain sites, particularly the other raphe nuclei, might play a role in this rigidity. Therefore, a study was performed in which 57 rats, divided into four groups, were implanted with chronic guide cannulae directed at brain sites anterior, lateral, or posterior to the RPn. After each animal was pretreated with intracerebral injections of MN, alfentanil (0.5 mg/kg) was administered subcutaneously. Electromyographic activity was recorded from the gastrocnemius muscle as a measure of hindlimb rigidity. Each animal was subsequently injected at 4 to 5 day intervals with MN two additional times at sites 1 and 2 mm deeper, respectively, than the initial injection. Data were thus obtained on animals treated with either MN or saline at 3 successive histologically identified sites which were either anterior, lateral or posterior to the RPn. The administration of MN into two specific sites in the region just lateral to the nucleus raphe pontis significantly [F(1,38) = 18.68 and 5.02 respectively, p less than 0.05] reversed the rigidity produced by systemic alfentanil administration. There was a weak effect of MN injections anterior to the RPn but this could not be localized to any one site. These results suggest that discrete brainstem regions involved in opiate action can be sensitively and selectively identified by direct intracranial injections of a lipophobic opiate antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alfentanil; Animals; Brain Stem; Fentanyl; Muscle Rigidity; Naloxone; Quaternary Ammonium Compounds; Raphe Nuclei; Rats; Rats, Inbred Strains

Topics: Aged; Anesthesia; Fentanyl; Humans; Male; Muscle Rigidity; Naloxone; Time Factors

High-dose fentanyl anesthesia is widely used in cardiac surgery. Its immediate side-effects are well known. However, its late adverse effect manifested by extreme truncal rigidity, decreased chest wall compliance, hypoventilation, respiratory acidosis and hemodynamic instability is not sufficiently appreciated. Of 380 patients who underwent aortocoronary artery bypass under high-dose (100 micrograms/kg) fentanyl anesthesia, 29 (7.6%) developed the sudden onset of extreme thoracic and abdominal rigidity, leading to respiratory depression 2 to 6 h postoperative, after an apparently normal recovery from the anesthesia. In 15 patients, a high plasma level of fentanyl (5.2 to 7.8 ng/ml) correlated with the clinical events. Administration of naloxone or a muscle relaxant rapidly reversed this late complication of fentanyl, thought to be due to re-entry of fentanyl into plasma from deposits in adipose tissue, muscle and the GI tract, leading to a secondary peak in plasma fentanyl. It is more likely to be encountered when hypothermia, rewarming, and acidosis occur in the postoperative period. Awareness of this life-threatening complication is critical in patients undergoing surgery with fentanyl anesthesia.

Topics: Aged; Anesthesia, Intravenous; Coronary Artery Bypass; Female; Fentanyl; Humans; Male; Middle Aged; Muscle Rigidity; Naloxone; Peak Expiratory Flow Rate; Respiratory Insufficiency; Retrospective Studies; Time Factors

Topics: Adult; Anesthesia Recovery Period; Anesthesia, General; Fentanyl; Humans; Intervertebral Disc Displacement; Male; Muscle Rigidity; Naloxone

The new method described in this study was based on consecutive repeated measurements of the resistance of flexor and extensor muscles of the hind foot of the rat to forced flexions and extensions of the foot. Locomotor movements of the rat were restrained with a metaplex box which had a slot for the hind limb. The control muscle tone measured by this method was constant for more than 2 h, and amounted to approx. 25 g for flexor muscles, and approx. 45 g for extensors. Morphine (2.5, 5, 10, 20 mg/kg) enhanced dose-dependently the resistance of flexor muscles up to approx. 45 g, 70 g, 100 g and 140 g, respectively, and the resistance of extensors of the paw up to approx. 100 g, 140 g, 180 g and 240 g, respectively. Haloperidol (5 and 10 mg/kg) enhanced dose-dependently the resistance of flexor muscles up to approx. 45 g and 70 g, respectively, and that of extensors of the foot up to approx. 75 g and 120 g, respectively. Morphine rigidity, measured as resistance of respective muscles to forced movements, was almost completely inhibited by a consecutive injection of 0.2 mg/kg of naloxone. The new method seems to have considerable advantages in comparison with electromyographical (EMG) or other kinds of mechanographical measurements of the muscle tone.

Topics: Animals; Haloperidol; Male; Morphine; Muscle Rigidity; Muscle Tonus; Naloxone; Rats; Rats, Inbred Strains

Attempts to eliminate or reduce the rigidity induced with high-dose narcotic anesthesia in the operating room have been only partially successful. Previous investigations of opioid receptor sites mediating this rigidity have implicated two central regions: the nucleus raphe pontis (NRP) within the reticular formation and the caudate nucleus (CN) within the basal ganglia. The present study used systemically administered alfentanil (ALF), a potent, short-acting fentanyl analog, and intracerebrally infused methylnaloxonium (MN), a quaternary derivative of naloxone, to elucidate further the functional role of the NRP and CN in rigidity. ALF (0.5 mg/kg s.c.) produced a reliable model of rigidity, as documented by gastrocnemius electromyography. The onset of this rigidity was within 60 s of ALF administration, with a total duration of approximately 40-50 min. Intracerebroventricular (i.c.v.) injections of 2.0 or 4.0 micrograms of MN 15 min prior to ALF treatment prevented rigidity, while 0.125 or 0.5 microgram had no significant effect on rigidity. MN injected directly into the NRP at doses as low as 0.125 microgram significantly antagonized ALF-induced rigidity, while injections of MN into the caudate nucleus at doses as high as 4.0 micrograms failed to antagonize ALF-induced rigidity. These observations demonstrate that injection of MN into the NRP is at least 16-fold more effective in blocking ALF-induced rigidity than MN injected into the ventricle and, more importantly, at least 32-fold more effective than MN injected into the CN. The results suggest that the NRP may be an important site for the neural control of muscular rigidity associated with high-dose narcotic administration.

Topics: Alfentanil; Animals; Catatonia; Caudate Nucleus; Electromyography; Fentanyl; Male; Muscle Rigidity; Naloxone; Pons; Quaternary Ammonium Compounds; Raphe Nuclei; Rats; Rats, Inbred Strains

A case of thoraco-abdominal rigidity leading to respiratory failure is described in the post-operative period in an elderly patient who received a moderate dose of fentanyl. This was successfully reversed by naloxone. The mechanisms possibly implicated in this accident are discussed.

Topics: Aged; Anesthesia; Female; Fentanyl; Humans; Muscle Rigidity; Naloxone; Nitrous Oxide; Postoperative Complications

The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS/KS group might be due to rapid shifts in the predominance of various DA-innervated structures.

Topics: Animals; Drug Tolerance; Haloperidol; Male; Morphine; Motor Activity; Muscle Rigidity; Naloxone; Rats; Rats, Inbred Strains; Receptors, Dopamine; Stereotyped Behavior; Time Factors

Topics: Acute Disease; Adult; Anesthesia, General; Anesthetics; Apnea; Coma; Fentanyl; Humans; Male; Muscle Rigidity; Naloxone; Postoperative Complications; Respiratory Insufficiency; Sufentanil; Time Factors

Systemic morphine induces explosive motor behavior and generalized muscular rigidity in frogs. Naloxone does not reverse either of these effects of morphine but at high doses causes muscular flaccidity and unresponsiveness to stimulation. Intraspinal morphine induces rigidity, but not explosive motor behavior, and this action is blocked by naloxone. Behavioral effects are seen rarely after intraspinal levorphanol (rigidity) and never after intraspinal dextrorphan or naloxone. In contrast to systemic morphine and naloxone, systemic levorphanol and dextrorphan are lethal to frogs at high doses.

Topics: Animals; Behavior, Animal; Dextrorphan; Injections, Subcutaneous; Levorphanol; Morphine; Motor Activity; Muscle Rigidity; Naloxone; Narcotics; Rana pipiens; Time Factors

Topics: Aged; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Levodopa; Male; Middle Aged; Movement Disorders; Muscle Rigidity; Naloxone; Parkinson Disease; Receptors, Dopamine

Topics: Animals; Female; Injections, Intraventricular; Morphine; MSH Release-Inhibiting Hormone; Muscle Rigidity; Muscle Tonus; Naloxone; Naltrexone; Rats; Rats, Inbred Strains; Time Factors; Tremor; Tremorine

Topics: Adult; Alphaprodine; Female; Humans; Muscle Rigidity; Naloxone; Respiratory Paralysis

Systemic administrations of opioids are known to induce "catatonia" or "lead pipe rigidity" in rats. The relevance of the caudate nucleus in inducing rigidity was tested. For this purpose, several opioids (or saline) were injected into the head of the caudate nucleus ("intrastriatal" injection) through an implanted cannula, and the electromyographical activity (EMG) was recorded in the gastrocnemius-soleus muscle (GS). Morphine (7.5-3.0 microgram), injected unilaterally, induced a continuous EMG activity in the ipsilateral GS muscle. This effect could be antagonized by systemic administration of naloxone (1 or 2 mg/kg i.p.). D-ala2-met5-enkephalinamide (3 microgram) and levorphanol (22.5 microgram) induced an EMG activity, too, whereas an equimolar dose of dextrorphan was ineffective, indicating that this effect was stereospecific and mediated via opioid receptors in the caudate nucleus. The EMG activity observed after systemic morphine administration (15 mg/kg i.p.) was antagonized by intrastriatal injection of naloxone (5 microgram). From our results, it can be concluded that the striatum--at least the head of the caudate nucleus--plays an important role in mediating the rigidity observed after systemic administration of morphine and other opioids.

Topics: Animals; Caudate Nucleus; Corpus Callosum; Electromyography; Male; Morphine; Muscle Rigidity; Muscles; Naloxone; Rats; Receptors, Opioid

Topics: Animals; Apomorphine; Dihydroxyphenylalanine; Dopamine; Dose-Response Relationship, Drug; Electromyography; Male; Morphine; Muscle Rigidity; Naloxone; Narcotic Antagonists; Rats; Time Factors