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At least 19 recordsLinked to original sources
PubMed1977

Naloxone-precipitated withdrawal as a function of the morphine-naloxone interval.

Withdrawal was precipitated by naloxone at different intervals, up to 22.5 h, following a last maintenance injection in morphine-dependent rats. Different symptoms of withdrawal were found to be preeminent following different morphine-naloxone intervals. Locomotor activity, jumping, and writhing were precipitated most frequently at shorter intervals after the last morphine injection; teeth chattering, wet dog shakes, ptosis, diarrhea, penile ejaculation, and hypothermia, at longer intervals. Others, including hostility, rhinnorhea and lacrimation did not change in frequency over the intervals measured. This order closely resembled that in which symptoms occurred as a result of withdrawal abstinence alone, though they were somewhat advanced in time. The results were discussed in relation to previously reported observations of naloxone-precipitated withdrawal, and in terms of their implications for a general theory of morphine withdrawal.

Animals↗
PubMed1979

Perinatal naloxone: when does naloxone affect hyperalgesia?

Pregnant mice were treated with naloxone via subcutaneous implants, from about 5 days prior to parturition. At birth entire litters were cross-fostered so that groups of offspring were exposed to naloxone treated mothers; before birth, after birth to weaning, from about 5 days prior to birth to weaning, or not exposed to naloxone. When tested on a hot-plate at 50 days of age, females either prenatally treated or treated pre- and postnatally showed hyperalgesia to heat. For males, this effect was not evident. This sex difference may have been induced by the cross-fostering procedure.

Aging↗
PubMed1977

Effects of naloxone on pethidine-induced neonatal depression. Part I--Intravenous naloxone.

Infants whose mothers had had pethidine during labour were given either naloxone 40 microgram or isotonic saline administered intravenously double-blind within one minute of birth. Peak alveolar carbon dioxide tension, carbon dioxide excretion, alveolar ventilation, feeding behaviour, and habituation to a specific sound stimulus were measured regularly up to 48 hours after birth. Alveolar carbon dioxide tension was significantly lower and alveolar ventilation significantly higher half an hour after birth in the naloxone-treated group than in the saline-treated group, but these differences between the groups were not significant at any other time, and there were no significant differences in sucking frequency or pressure, milk consumption, or habituation to the auditory stimulus.

Clinical Trials as Topic↗
PubMedDate not supplied

Enhanced naloxone distribution to the brain by morphine pretreatment in mice.

An increase in the disposition of naloxone to the mouse brain was observed for animals previously exposed to morphine. Compared to controls, mice receiving morphine sulfate (10 mg/kg, sc) 3 hr prior to naloxone had a 28% increase in naloxone concentration in brain (200 to 260 pmol of naloxone per g of brain) 10 min after 3H-naloxone-HCl (0.4 mg/kg, 11.0 micronCi/kg, sc) administration. Also, if similar morphine-pretreated mice received a second dose of morphine sulfate (1.0 mg/kg, sc) concurrent with 3H-naloxone-HCl, the morphine-induced enhancement of 3H-naloxone concentration in brain was unaltered. This drug-treatment protocol paralleled that used by others in pA2-analgesia assays to demonstrate sensitization to naloxone for morphine-pretreated animals. In prior (3 hr) morphine-treated animals, administration of 3H-naloxone-HCl (0.1 mg/kg, 33.3 micronCi/kg) iv resulted in an 11.0% increase in 3H-naloxone brain concentration after 1 min. Thus, the enhancement of naloxone brain concentration was independent of the route of naloxone administration. No enhancement of 3H-naloxone brain concentration could be seen 24 hr after morphine sulfate pretreatment (10 mg/kg, sc), a decline in the effect similar to that seen for morphine-induced sensitization to naloxone. Finally, when morphine pellet-implanted mice (75 mg of morphine base, 72 hr) were administered 3H-naloxone-HCl (0.4 mg/kg, 10.0 micronCi/kg, sc), only a 22.5% enhancement of 3H-naloxone concentration in brain was obtained, as opposed to a reported 8-fold increase in the potency of naloxone. Thus, although a number of similarities exist between the enhancement by morphine of naloxone concentration in brain and its sensitization to the antagonistic activity of naloxone, a quantitative correlation appears to be lacking between the two phenomena.

Animals↗
PubMed1977

Antagonism of fentanyl with naloxone during N2O+O2+ halothane anaesthesia.

To investigate the antagonistic effect of naloxone on fentanyl-induced respiratory depression, 55 patients (randomly divided into various study and control groups were studied during nitrous-oxide-oxygen-halothane anaesthesia. Respiratory depression after 0.1 mg of fentanyl was totally reversed by 10 microgram/kg of naloxone, measured as 100% restoration of spontaneous respiration, normal minute volume and end-tidal CO2, while 15 microgram/kg of naloxone was needed to antagonize 0.2 mg of fentanyl. The respective control groups remained apnoeic. If no fentanyl had previously been administered, there was no difference in the respiratory behaviour of naloxone-treated and control patients, which indicates that no unspecific analeptic effect of naloxone could be demonstrated. The circulatory changes after fentanyl were nearly reversed by naloxone, as has been found earlier with other narcotics. Recovery from anaesthesia was scored from 0 to 10 (using a modification of Apgar scores for newborns), and somewhat higher mean scores were obtained with the naloxone-treated patients than with their controls. However, higher postoperative pain scores were recorded in these patients as well as a higher incidence of nausea and vomiting. The study demonstrates the dose-relationships of fetanyl and naloxone for estimation of total antagonism; however, the use of naloxone for partial antagonism at the termination of anaesthesia cannot be based on these findings.

Adult↗
PubMed1977

Naloxone as narcotic antagonist after balanced anaesthesia.

Different modes of naloxone administration were studied in 100 patients following N2O-O2-relaxant anaesthesia, where fentanyl was administered for analgesia according to a standardized dose schedule (mean 4.3 microgram/kg/h). After reversal of muscular relaxation, the patients were randomly given naloxone--either 1.0 or 2.5 microgram/kg i.v. or 2.5 or 5.0 microgram/kg i.m., or none (control). Each group consisted of 20 patients. Awakening was fastest after 2.5 microgram/kg i.v. of naloxone (1.8 +/- 0.1 min), the time being significantly shorter (P less than 0.025) than in the control group (2.7 +/- 0.4 min). After 15 min, the minute volume and frequency of respiration were significantly higher (P less than 0.05) in all naloxone groups than in the control group. However, the arterialized venous PCO2 did not show significant differences during the recovery. It is therefore suggested that naloxone reversal may cause an increase in CO2 production. The immediate postoperative pain (score 0-3) was mildest in the control group (1.0 mean) and severest after 2.5 microgram/kg i.v. of naloxone (1.8 mean); the difference was statistically significant (P less than 0.05). The groups receiving 1.0 microgram/kg i.v. and 2.5 microgram/kg i.m. did not differ from each other (1.2 mean). Nausea and vomiting were reported more often after 5.0 microgram/kg im. of naloxone than in other groups. After moderate doses of fentanyl during balanced anaesthesia, routine use of naloxone does not seem to be necessary, but if rapid recovery is essential, 1.0 microgram/kg i.v. or 2.5 microgram/kg i.m. of naloxone may be recommended and these doses do not cause a higher incidence of side effects.

Adjuvants, Anesthesia↗
PubMed1978

[Naloxone--a clinical study on dosage (author's transl)].

In 50 Patients (group I) anaesthetized with neuroleptanalgesia and in 20 patients (group II) anaesthetized with moderate doses of fentanyl given to supplement nitrous oxide - halothane anaesthesia the postoperative respiratory depression was antagonized with naloxone. Each patient was carefully titrated with small increments of naloxone (40 microgram) given in 1-2 minute intervals. A reversal of the narcotic induced respiratory depression was taken for granted, when respiratory rate exceeded 12/min, tidal volume and blood gas analysis showed normal values. The results demonstrated a correlation between the need for naloxone and the time interval from the last administration of fentanyl to the completion of the operation and the fentanyl consumption per hour. When the interval was less than 1 hour more than 90% of the patients required postsurgical naloxone for respiratory inadequacy. The mean naloxone dose was 20 to 30% of the fentanyl dose given per hour: 1,2 microgram/kg naloxone reversed 4,9 microgram/kg.h fentanyl (group I) and 0,6 microgram/kg naloxone reversed 2,9 microgram/kg.h fentanyl (group II) respectively. To prevent renarcotization it is recommended to administer naloxone i.m. 30 to 45 min after the last naloxone-injection using the total i.v. dose.

Adolescent↗
PubMed1979

Naloxone effects on schedule-controlled behavior in morphine-pelleted rats.

The effects of morphine pellet implantation and naloxone administration were examined in rats lever pressing under inter-response time schedules of food presentation. Subcutaneous implantation of a morphine pellet initially decreased lever-pressing rates. Tolerance to this effect developed within 3--4 days. Naloxone (0.25--1.0 mg/kg) decreased response rates in morphine-pelleted rats in a dose-dependent and time-dependent manner. All doses of naloxone severely decreased rates of lever pressing on days four to nine post-pellet. This rate-decreasing effect persisted 7--17 days for 0.25 mg/kg naloxone, 9--22 days for 0.50 mg/kg, and 13--28 days for 1.0 mg/kg. Decreases in response rate were due to an increased frequency of long pauses and not to marked shifts in the temporal patterning of those lever presses that did occur. Changes in response rate after naloxone were accompanied by body weight loss. Area values summarizing the naloxone-induced changes in response rate or body weight over time after pellet implantation increased as a function of naloxone dose. Naloxone (0.25--1.0 mg/kg) did not alter performance by placebo-pelleted rats.

Animals↗
PubMed1979

Suppression of deprivation-induced food and water intake in rats and mice by naloxone.

Naloxone, an opiate antagonist, was administered to male and female rats and male mice after periods of food or water deprivation ranging from 12 to 48 hr. Naloxone (0.01-10 mg/kg) reduced postdeprivational water intake in most groups of rats and mice in a dose-related manner. Naloxone suppression of water consumption appeared to be independent of sexual differences in rats, and phase of the diurnal cycle, and length of the deprivation interval in both rats and mice. Postdeprivational food intake in male rats and mice was also reduced by naloxone in a dose-dependent fashion. This naloxone effect was less pronounced than actions observed with water intake, and tended to diminish with lengthening food deprivation periods. In general, mice appeared to be less sensitive than rats to naloxone suppression of food and water intake. Naloxone appears to markedly reduce appetitive behavior, particularly water intake, following deprivation in both rats and mice. The fact that low doses of naloxone can elicit these effects suggests that the drug is acting at specific tissue sites, possibly endorphine recpetors.

Animals↗
PubMed1979

Naloxone reversal of mild neurobehavioral depression in normal newborn infants after routine obstetric analgesia.

To investigate the presence of subtle narcotic depression following maternal narcotic analgesia, we have evaluated the effects of naloxone versus placebo in a double-blind parallel group study in 43 normal term newborn infants whose mothers had received routine narcotic analgesia within six hours prior to delivery. Infants were given either an intramuscular injection of 20 microgram/kg naloxone or 0.20 ml/kg placebo after determination of the one-minute Apgar score, and the following measurements were compared: Apgar scores at one and five minutes, capillary blood gas values at one, 60, 120, and 240 minutes, and neurobehavioral assessments at one, 4, and 24 hours. No adverse effects from naloxone were observed. Neither Apgar scores nor capillary blood gas determinations differed significantly between the two groups. Response to sound was significantly higher in the naloxone group at 24 hours. The alertness score was significantly higher for the naloxone group at one and four hours; the general assessment score for the naloxone group was significantly higher at four and 24 hours. Average scores of naloxone and placebo groups were also different at four and 24 hours of age. These data demonstrate that maternal narcotic analgesia may produce subtle changes in alertness and general behavior not reflected by Apgar scores or respiratory status, potentially reversible by administration of naloxone shortly following delivery.

Anesthesia, Obstetrical↗
PubMed1976

Morphine, pentazocine and naloxone effects on responding under a multiple schedule of reinforcement in rhesus monkeys and pigeons.

The effects of morphine, pentazocine, naloxone and combinations of these drugs on schedule-controlled behavior were examined in rhesus monkeys and pigeons. The order of potency in decreasing response rates under a multiple 5-minute fixed-interval, 30-response fixed-ratio schedule in both monkeys and pigeons was morphine greater than pentazocine greater than naloxone. Compared to monkeys, pigeons were less sensitive to morphine and pentazocine and slightly more sensitive to naloxone. In monkeys and pigeons, as the morphine dose increased, higher naloxone doses were required to restore responding to or near control levels. In pigeons, however, the response rate decreases caused by naloxone prevented the complete antagonism of the highest morphine dose and limited the range of naloxone doses over which complete antagonism of morphine occurred. Antagonism of pentazocine by naloxone generally was greatest at the lowest pentazocine dose tested in both monkeys and pigeons. At higher pentazocine doses, if any antagonism was obtained, it was slight, and the amount of antagonism typically did not increase as the naloxone dose increased. Pentazocine generally failed to antagonize morphine in monkeys and pigeons.

Animals↗
PubMed1976

Morphine-based secondary reinforcement: effects of different doses of naloxone.

The effects of different doses of naloxone on morphine-based secondary reinforcement were studied in rats. On the first day a neutral stimulus (buzzer) was repeatedly paired with intravenous morphine infusions. Drug treatments consisted of Low, Medium, or High Naloxone doses, or No Naloxone. The next day the ability of the buzzer and saline infusion to support lever pressing was tested. High Naloxone blocked, and Low Naloxone partially blocked this morphine-based secondary reinforcement. Subjects in the Medium Naloxone group demonstrated an apparent avoidance of the lever, suggesting that the morphine infusions were aversive at this dosage level of naloxone. The secondary reinforcement tests reliably predicted behavior on a subsequent test for acquisition of morphine-seeking behavior.

Animals↗
PubMed1979

Further studies on the role of cholinergic mechanisms in the development of increased naloxone potency in mice.

Using the abdominal constriction response in mice, it was shown that pretreatment with either pilocarpine (5.0 mg/kg, s.c.) or oxotremorine (0.05--0.10 mg/kg s.c) caused a small but significant potentiation of the antinociceptive effect of morphine and the antagonistic action of naloxone. The potentiation of naloxone was considerably augmented following pretreatment with morphine plus either pilocarpine (2.5--5.0 mg/kg) or oxotremorine (0.05--0.10 mg/kg) as compared with any of these drugs given alone. Pretreatment with atropine sulphate (2.0 mg/kg, s.c.) had no effect on naloxone potency nor on the antinociceptive activity of morphine, but somewhat reduced that of pilocarpine and oxotremorine. Atropine abolished the ability of morphine pretreatment to enhance naloxone potency, and greatly reduced the augmenting effect of morphine plus the muscarinic receptor agonist drugs. It was also shown that oxotremorine reduced the development of dependence on morphine as tested by naloxone-precipitated jumping. These results agreed well with those reported using anticholinesterase drugs and add further evidence that the cholinergic system does play a role in the development of increased naloxone potency caused by morphine pretreatment. The increased naloxone potency does not seem to be related to the development of "acute dependence" on morphine.

Abdominal Muscles↗
PubMed1979

Toxic interactions of ethanol with other central depressants: antagonism by naloxone to narcosis and lethality.

The effects of naloxone on narcosis and/or lethality induced by diazepam, lithium, methaqualone and phenobarbital either alone or in combination with ethanol were studied in mice. Interaction toxicities between ethanol and the various psychotropic drugs were dose-dependent and so was the degree of antagonism by naloxone. Treatment with phenobarbital (10 mg/kg) or methaqualone (50 mg/kg) or lithium (4 meq/kg) prolonged the narcosis induced by ethanol (5 g/kg) by 45, 269 and 107% respectively. Naloxone (10 mg/kg) shortened the ethanol (5 g/kg) induced narcosis by 38%. Naloxone (10 mg/kg) also shortened narcosis induced by ethanol (5 g/kg) in combination with phenobarbital (10 mg/kg) or methaqualone (50 mg/kg) or lithium (2meq/kg) by 31, 12 and 38% respectively. At 10 mg/kg of naloxone, the LD50 due to methaqualone was increased from 240 mg/kg to 416 mg/kg, and the LD50 due to ethanol was increased from 9.2 g/kg to 10.8 g/kg. Multiple injections of naloxone significantly (p less than 0.01) protected against the lethality of phenobarbital but not that of lithium. These findings provide further evidence of naloxone antagonism towards various CNS depressants.

Animals↗
PubMed1979

Restlessness and shivering after naloxone reversal of fentanyl-supplemented anaesthesia.

To study the significance of normalization of ventilatory or thermal homeostasis during naloxone reversal, 95 patients were given naloxone after thiopental-N2O-O2-relaxant anaesthesia supplemented with fentanyl (6 microgram/kg/h). If naloxone 0.16 mg was given to combat postoperative apnoea during hypercapnia (end tidal carbon dioxide concentration (ETco2)8%), minute ventilation and respiratory rate were significantly higher during the first minutes as compared to the normocapnic patients. Shivering occurred in 44% in the hypercapnic group, as compared to about 30% if naloxone was given during normocapnia (ETco2 5%). Postoperative pain and restlessness were significantly increased in the hypercapnic group. During normocapnia, untoward reactions were less frequent (40%) if naloxone was given in smaller increments (0.08 + 0.08 mg) rather than in one dose (0.16 mg) (72%). This was mainly due to nausea (8% compared to 32%). The incidence and severity of shivering showed a positive correlation to the duration of anaesthesia (r = 0.42) and to the total amount of fentanyl (r = 0.32), but not to the actual postoperative oesophageal temperature (r = -0.13). The results indicate that though untoward reactions after naloxone reversal are aggravated by naloxone-induced normalization of deranged homeostatic mechanisms, their aetiology probably should be sought in an acute abstinence syndrome.

Adult↗
PubMed1978

[Respiratory depression after fentanyl and antagonism by naloxone (author's transl)].

The postoperative respiratory depressant effect of fentanyl in combination with flunitrazepam (Rohypnol) was assessed in awake and in unconscious patients. In awake patients respiratory function was measured with blood-gas analyses. For measurements in unconscious patients the administration of nitrous oxide/oxygen was continued postoperatively and the respiratory depression was judged from the increase in respiratory minute volume after the i.v. administration of 0.05 mg naloxone (Narcan). In the group of awake patients blood-gasvalues were within the normal range after anaesthesia with flunitrazepam (1 mg) and fentanyl (0.80 mcg/kg body weight/10 min anaesthesia; last fentanyl given 40 min before the end of the operation), and the administration of naloxone was without any effect. If, however, naloxone was given while the patients were kept under light nitrous oxide/oxygen anaesthesia, the effect was different. The respiratory minute volume was considerably less than its predicted value in all groups of patients having received fentanyl, and naloxone caused a marked increase in respiratory minute volume and in respiratory rate. In a group of patients which have received no opiate but enflurane, naloxone showed no effect. After premedication with pethidine as compared with flunitrazepam the effect of naloxone on ventilation was more pronounced. This marked difference in the postoperative effect of fentanyl on ventilation depending on the state of consciousness has to be attributed to an interaction between a residual respiratory depressant effect of fentanyl and the effect of unconsciousness. Since after the combined use of flunitrazepam and fentanyl deep postoperative sleep occurs quite frequent, a residual effect of fentanyl should always be antagonized with naloxone to protect the patients from a possible hazardous effect of this interaction.

Adolescent↗
PubMed1976

Effects of morphine alone and in combination with naloxone or d-amphetamine on shock-maintained behavior in the squirrel monkey.

Key-pressing behavior in the squirrel monkey was maintained under an 8-min fixed-interval (FI) schedule of electric-shock delivery. The acute i.m. administration of morphine prior to a daily session decreased response rates at doses of 1.0--3.0 mg/kg but had little systematic effect on rate at doses of 0.03-0.3 mg/kg. When naloxone was administered concomitantly with morphine prior to a session, 0.01 mg/kg naloxone required a three-fold increase in the dose of morphine necessary to obtain decreased response rates, 0.1 mg/kg naloxone required a 30-fold increase in morphine, and 1.0 mg/kg required more than a 30-fold increase in morphine. Moreover, the administration of naloxone with morphine resulted in increased rates of responding at certain combinations of doses of the two drugs. The administration of d-amphetamine (0.03 or 0.1 mg/kg) alone increased mean response rates under the FI schedule; when combined with 0.03-0.3 mg/kg morphine the increases in responding were greater than obtained with d-amphetamine alone. The negative slope of the linear regression lines relating the effects of morphine to control rates of responding engendered under the FI schedule was decreased when morphine was combined with naloxone, but not with d-amphetamine. These results show that naloxone, but not d-amphetamine, can antagonize the response-rate decreasing effect of morphine when responding in the squirrel monkey is maintained by response-produced electric shock.

Animals↗