Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The addition of d-amphetamine to morphine has been reported to result in an increase of analgesic potency in experimental animals and man, but no data on the toxicity of such combinations are available. This study is intended to provide systematic information on the toxicity, analgesic potency and degree of physical impairment (swimming endurance) of a combination of 12 mg morphine sulfate with 10 mg d-amphetamine HCl per ml which is now under clinical investigation. Mice were used as experimental subjects. Meperidine, methadone and pentazocine were substituted for morphine using clinically equally analgesic doses and keeping the d-amphetamine amount constant. The toxicity of all analgesics especially that of morphine was enhanced in the combination, least so in the case of meperidine. The degree of increase of analgesic power by the addition of d-amphetamine was greatest with morphine and quantitatively in satisfactory agreement with present clinical experiences. However, the relationship between the increases of toxicity and of analgesia is not necessarily most favorable for this drug. For the other three analgesics increases in toxicity and analgesia were more in line, meperidine showing the best ratio. Swimming endurance was decreased with full analgesic doses of all four compounds. The presence of d-amphetamine tended to reverse this depression. The data were analyzed in relation to their possible predictive value for the use of such combinations in man for the therapeutic dose range and in the event of overdosage.
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PMID:A study of the effect of d-amphetamine on the toxicity, analgesic potency and swimming impairment caused by potent analgesics in mice. 24 3

In a dose-response study, 7.5 mg/kg of naloxone produced maximal attenuation of conditioned taste aversion to saccharin induced by 10 mg/kg of morphine. Naloxone was administered immediately after the morphine in this study. In a second experiment, naloxone still caused a significant attenuation of taste aversions when administered with a 1 hr delay after morphine, but not after delays of 4 or 8 hr. These results suggest that behavioral consequences of morphine which peak during the first hr after injection (analgesia, catalepsy, and depression of intracranial self-stimulation) are not correlated with the aversive effect of morphine. Nor can the aversiveness of morphine be attributed to withdrawal effects. Only the facilitative actions of morphine occurring 1 to 4 hr after injection, including the facilitation of intracranial self-stimulation, are temporally correlated with the naloxone-sensitive aversive effect. Thus, a temporal analysis cannot be used to dissociate the paradoxical positive reinforcement and aversive effects of morphine. Rather, the temporal correlation between the two opposite motivational effects of morphine serves to emphasize the nature of this paradox.
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PMID:Temporal analysis of naloxone attenuation of morphine-induced taste aversion. 26 68

Pethidine is commonly used in single doses as a preoperative medication or in multiple doses as an analgesic. The clinical consequences of altered disposition are more likely to result from its analgesic use. Correlations between plasma pethidine concentration, analgesia and side effects such as respiratory depression, have been established, but considerable overlap exists between concentrations producing therapeutic and non-therapeutic effects. The current practice of intermittent pethidine administration (intravenous, intramuscular and oral) for analgesia results in fluctuations in pethidine plasma concentrations which are associated with incomplete pain relief and side effects. Continuous intravenous infusion of pethidine may avoid these difficulties. Changes in pethidine disposition have been observed in patients with liver disease and in the elderly. Measurement of plasma pethidine concentrations may be helpful as an aid to the management of such patients. In renal disease, metabolites may accumulate and cause side effects.
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PMID:Clinical pharmacokinetics of pethidine. 35 12

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.
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PMID:Naloxone reversal of mild neurobehavioral depression in normal newborn infants after routine obstetric analgesia. 36 95

In a population of 61 surgical patients, 10 and 15 mg dezocine were compared with meperidine 100 mg for relief of postoperative pain. Pain relief experienced by the patient and pain intensity evaluated by a nurse and a physician displayed similar characteristics: dezocine 10 mg was less effective than meperidine but dezocine 15 mg showed a rapid onset of analgesic effect with a longlasting analgesia superior to meperidine. Vital signs remained stable within satisfactory limits with no respiratory depression occurring. Blood-gas analysis showed a significant but comparable increase in PaCO2 with slight decrease of PaO2 in all patients treated with dezocine or meperidine. Side effects observed included an overt sedative effect of both analgesics, which for dezocine appeared to be dose-related.
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PMID:Analgesic properties of dezocine for relief of postoperative pain. 39 27

A series of tetrahydro- and hexahydrocannabinol derivatives was prepared in which the substituents at position 9 were varied. These compounds were evaluated in mice for their effects on locomotor acitivty, body temperature, muscle tone, and analgesia. Depression of body temperature and locomotor function was demonstrated by several compounds, but all were devoid of any significant analgesic activity.
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PMID:Structure--activity studies on tetrahydro- and hexahydrocannabinol derivatives. 42 21

The guinea pig is notoriously difficult to anesthetize with conventional agents. Cardiorespiratory depression by general depressant anesthetic agents can render the cochlea abnormal. I report a technique that uses the specific neuroleptic and analgesia properties of the agents droperidol and phenoperidine, respectively, in combination with small doses of pentobarbital sodium, which is required only to produce unconsciousness. These agents can be given intraperitoneally, intramuscularly, or intravenously. The regimen allows performance of substantial surgery (including intracranial) and long-term (minimum, six to ten hours) physiological studies, such as those on the cochlea, with excellent cardiorespiratory stability. The method has been in continuous use in this laboratory since 1974 for single-fiber recordings from the cochlear nerve of normal and kanamycin-treated guinea pigs. This method has proved to be substantially more effective than use of pentobarbital, thiopental sodium, urethan, chloralose, or ketamine alone.
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PMID:Neuroleptanesthesia for the guinea pig. An ideal anesthetic procedure for long-term physiological studies of the cochlea. 42 4

In a randomised trial postoperative pain relief was provided by either epidural injections of bupivacaine or an infusion of fentanyl adjusted by the patient to achieve adequate pain relief. Both techniques produced satisfactory analgesia without respiratory depression after peripheral arterial surgery. The technique of infusing intravenously a potent analgesic in a dose adjusted by the patient appears to offer several advantages in postoperative care.
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PMID:Postoperative analgesia: a comparison of intravenous on-demand fentanyl with epidural bupivacaine. 46 35

Morphine and morphine-related agents were applied by microiontophoresis in the lumbar spinal cord of spinal cats to single units classified on the basis of their responses to natural cutaneous or proprioceptive stimulation. Opiate application had a current-dependent depressant effect on the ongoing activities of about one-third of the units tested. This effect was observed in laminae I and IV--VI, but only with units responding to noxious cutaneous stimuli: the nociceptive responses were themselves depressed. Excitatory and inhibitory responses to glutamate and gamma-aminobutyric acid, respectively, were also depressed. Intravenous administration of the opiates at doses reported to produce analgesia in the cat also depressed only units responding to noxious cutaneous stimuli, including their nociceptive responses. This depression could be reversed by either the iontophoretic application (100 nA) or the intravenous administration (0.1--0.8 mg/kg) of naloxone. These results are interpreted as further evidence that the analgesic effects of opiates are at least partly due to an action at the spinal level.
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PMID:Action of narcotic analgesics and antagonists on spinal units responding to natural stimulation in the cat. 48 72

Bupivacaine, 0.125 per cent, with epinephrine, 1:800,000, was administered to 3,000 women in labor. Administration was in the lumbar epidural space for the purpose of achieving satisfactory analgesia with minimal or no motor paralysis. The usual initial dose of 12.5 mg (mean 13 +/- 2 SD) resulted in good sensory analgesia in 83 per cent of the patients and lasted for about and hour (mean 58 +/- 16 min). The mean total dose used for labor and delivery was 55 +/- 20 mg and the mean dose per hour 23 +/- 13 mg. Satisfactory analgesia for labor and delivery was obtained in 92 per cent of the patients, and in 66 per cent there was no discernible motor blockade. In the 3,000 patients, there was no adverse reaction to bupivacaine or epinephrine. No patient had a total spinal block or neurologic sequelae, and no neonatal depression could be attributed to the anesthetic.
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PMID:Bupivacaine, 0.125 per cent, in obstetric epidural analgesia: experience in three thousand cases. 49 59


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