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)

Butorphanol, a new, totally synthetic morphinan, which is chemically related to naloxone, has been demonstrated to have both analgesic and narcotic antagonist properties. In rodent antiwrithing analgesic tests, butorphanol was 4 to 30 times more potent than morphine and dl-pentazocine, respectively. As an antagonist, butorphanol was about equivalent to nalorphine and 30 times more potent than dl-pentazocine. On the basis of the naloxone-induced mouse jumping test and the lack of substitution in withdrawn morphine-dependent mice, it is estimated that the potential for physical dependence of butorphanol will be less than that of dl-pentazocine but greater than that of nalorphine and dl-cyclazocine. Animal data also show that agonistic actions of butorphanol, such as respiratory depression and miosis, reach ceiling effects which are lower than those seen with morphine with an increase in dosage. Thus, butorphanol differed from morphine which exhibited agonist effects in a dose-related manner. Butorphanol showed weak to moderate central depressant properties at doses which were considerably higher (greater than 100 X) than those producing analgesia. Minimal cardiovascular and respiratory effects were seen with butorphanol in conscious dogs.
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PMID:The pharmacology of butorphanol, a 3,14-dihydroxymorphinan narcotic antagonist analgesic. 6 89

Narcotic analgesics and related drugs act as agonists on several receptors that are responsible for their effects on pain perception, mood and feeling state, and respiration, as well as other pharmacologic actions. Naloxone is the first discovered antagonist that is devoid of agonistic activity and appears to be a competitive antagonist at several receptors. The ability of naloxone to displace or prevent the binding of agonistic narcotics is partly responsible for its antagonistic effects. The ability of naloxone to rectify narcotic-depressed homeostats and precipitate abstinence is also related to its antagonistic activity. Certain cautions and principles apply in the use of naloxone in treating narcotic overdose, reversing surgical analgesia, and the treatment of neonates and children. Unapproved uses of naloxine include reversing the psychotomimetic effects of certain agonists-antagonists, terminating narcotic-induced convulsions and coma, reversing non-narcotic depression, diagnosing physical dependence, and treating narcotic addicts.
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PMID:Naloxone. 18 95

The effects of ethanol withdrawal were determined on cell free brain protein synthesis in physically dependent rats. Following the development of physical dependence, ethanol abstinence for 24 h resulted in decreased protein synthesis in cerebral tissue. The observed inhibition of [14C]leucine incorporation into protein was found to be reversible after 7 days of ethanol withdrawal. Although the ribosomes from control, ethanol-treated and ethanol-withdrawn animals were highly responsive to polyuridylic acid stimulation, the ribosomes from the control group consistently exhibited higher activity. The determination of protein content of the ribosomal fraction showed a significant increase following ethanol administration and was further enhanced by ethanol abstinence. The results suggest that ethanol-induced changes at the ribosomal level may result in defective association of mRNA causing depression of brain protein synthesis.
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PMID:Alterations in cell free brain protein synthesis following ethanol withdrawal in physically dependent rats. 55 14

A single administration of ifenprodil at the doses of 100, 200 and 400 mg/kg (p.o.), and 50 and 100 mg/kg (i.m.) produced a moderate CNS depression in rats, such as, sedation, ptosis, systemic muscle relaxation and decrease in motor activity. These symptoms appeared dose-dependently and persisted for about 4 hours following administration. In a direct physical dependence test, 5 groups of rats were fed the ifenprodil-admixed food together with drinking water ad libitum for 24 hours daily for 53 approximately 103 days (mean ifenprodil intake, 43--240 mg/kg/day), on the gradedly increased dosage schedule with a dosage level of 0.5 vs. 1 mg/g food to 4 mg/g food. In the natural withdrawal following administration, no significant withdrawal signs were observed in any group. In a substitution test either for phenobarbital or morphine, no suppression of withdrawal signs during the period of cross-administration of ifenprodil and no maintenance of dependence were observed. In a physical dependence-producing test, the rats fed ifenprodil never manifested withdrawal signs such as diarrhea, "wet shakes", sudden loss of body weight as in the levallorphan precipitation test. Ifenprodil apparently has no physical dependence liability.
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PMID:[Physical dependence liability test of ifenprodil in rats (author's transl)]. 56 49

This paper reports findings relative to a simple, rapid and reproducible technique for the induction of physical dependence upon ethanol in the rat. The dependence was induced by intragastric intubation of 20% (w/v) ethanol solutions at 9-15 g/kg in 3-5 fractional doses daily for 4 days, maintaining blood ethanol concentrations above a threshold level sufficient to sustain observable sedation throughout the entire period of intubation. Two phases were distinguished during the withdrawal period: 1. Prodromal detoxication, characterized by a spectrum of signs and responses of diminishing severity, related to the decline in blood ethanol concentrations (mg/dl): death, greater than 640; coma, 780-460; loss of righting reflex, 640-400; ataxia 3-1, 570-250; sedation 340-190; neutrality, 220-130; 2. Ethanol dependence, characterized by a spectrum of withdrawal signs and reactions of progressively increasing severity as blood ehtanol concentration approached 100 mg/dl: hyperactivity, tremors, akinesia, spastic rigidity, and induced and spontaneous convulsions. A rapid sucession of two diverse clusters of signs and reactions represents a reversal of the central nervous system function from the extremes of ethanol intoxication (CNS depression) to the extremes of ethanol dependence (CNS hyperexcitability) during the withdrawal period. Both extremes may terminate in death.
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PMID:Induction of physical dependence upon ethanol and the associated behavioral changes in rats. 123 14

Inadequately treated acute and chronic pain remains a major cause of suffering, in spite of enormous advances in pharmacology and technology. Opioids provide a powerful, versatile, widely available means of managing this pain, but their use is too often restrained by ignorance and mistaken fears of addiction. The management of postoperative pain (perhaps the most common form of acute pain) is traditionally attempted with fixed dosages of analgesics by relatively unpredictable routes (e.g. oral, rectal and intramuscular). Intravenous opioid infusions (an improvement) risk respiratory depression and require close monitoring and titration. Patient-controlled analgesia (PCA), by contrast, permits the most efficacious medication (pure opioid agonist) by the optimal route (intravenous) under direct control of the patient, and provides high levels of satisfaction and safety. Ideally, any opioid use should be integrated with a wide spectrum of other analgesic modalities in an anaesthesiology-based 'acute pain service'. The use of opioids for chronic pain of nonmalignant origin remains controversial. There is a perceived conflict between patients' interests and those of society. However, problems (such as tolerance, physical dependence, addiction and chronic toxicity), anticipated from experience with animal experiments and pain-free abusers, seldom cause difficulties when opioids are used appropriately to treat pain (so-called 'dual pharmacology'). With sensible guidelines, and in the context of a multidisciplinary pain clinic, opioids may provide the only hope of relief to many sufferers of chronic pain.
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PMID:Treatment principles for the use of opioids in pain of nonmalignant origin. 171 22

Buprenorphine is a mixed opioid agonist/antagonist which appears to produce less physical dependence and respiratory depression than typical mu-agonist opioids. These effects suggest its use for analgesia for drug abusers. However, buprenorphine may precipitate withdrawal from other opioids. The present case illustrates the utility of buprenorphine and describes a method to transfer a patient from a mu-agonist to buprenorphine without precipitating withdrawal or interrupting analgesia.
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PMID:Buprenorphine for pain relief in a patient with drug abuse. 174 7

To observe the dispositional and functional tolerance to and physical dependence on barbital, the influence of repeated administration of the drug on serum barbital levels, coordinative motion, body weight, and cortical evoked potential was assessed. Rats administered the first dose of barbital showed marked impairment of gross behavior and then loss of the righting reflex. While they were repeatedly treated with barbital for a 4-week period, the CNS depression became weaker and weaker, and loss of the righting reflex was no longer observed. Serum barbital levels after administration of barbital tended to decrease by the 28th day of repeated drug administration. Coordinative motion was markedly impaired after administration of the first dose, but gradually recovered during the repeated administration period. Barbital at 100 mg/kg, i.p., prolonged the latent time of the evoked potential in normal untreated rats but not in tolerant rats. During the withdrawal period, no particular change was observed in the animals' gross behavior. However, body weight loss and shortening of the latent time of the evoked potential were observed at 60 to 72 hours of withdrawal. These results suggest that cortical evoked potential can serve as a useful method for observing tolerance to and physical dependence on barbital.
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PMID:Observation of the development of tolerance to and physical dependence on barbital by cortical evoked potential in rats. 188 Sep 88

Physical and psychic dependence on opioids and CNS depressants in rodents were examined using the drug-admixed food (DAF) method. A comparison of several methods for developing physical dependence on opioids was made. The DAF method has the advantage of rapidly inducing a high degree of physical dependence without causing morbidity or mortality. When morphine-dependent rats were pretreated with several opioids, naloxone-precipitated weight loss was suppressed in a dose-dependent manner. A procedure for the development of severe physical dependence on CNS depressants was also established. Drug concentrations were rapidly increased until animals showed moderate to severe CNS depression, and then this condition was maintained for at least 10 days. With this procedure, animals became severely dependent on CNS depressants. Another technique, intermittent infusion, was developed that has been used to quantify short-acting CNS depressant dependence potential. The sedative effects of pentobarbital were used as an index in the determination of the injection intervals. These results suggest that the DAF method and the new approaches are useful tools for assessing the physical dependence potential of new drugs. Moreover, oral self-administration and weight pulling procedures were utilized along with the DAF method. Procedures for the oral self-administration of opioids and CNS depressants were established. Opioid-dependent rats pulled the weight to obtain the DAF even though they had free access to normal food. This weight-pulling procedure may be useful for assessing the degree of reinforcing effects for drugs in rats.
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PMID:Pharmacological studies on drug dependence in rodents: dependence on opioids and CNS depressants. 240 80

The effect of three dosage schedules on the expression of a withdrawal syndrome indicative of physical dependence on pentobarbital was determined in male Sprague-Dawley rats. Rats were prepared with an intraperitoneal cannula and were continuously infused with either saline (control) or pentobarbital sodium, using an escalating drug dosage schedule, for either 5 (PB-5), 13 (PB-13) or 20 (PB-20) days. Final doses reached were 500 mg/kg/day (PB-5) and 1000 mg/kg/day (PB-13). PB-20 rats reached 1000 mg/kg/day on day 13 and were maintained at this dose for an additional 7 days. Body weight, water consumption and assessment of CNS depression were obtained daily. Following the last day of pentobarbital infusion all rats were infused with saline for a 72-hour drug-free period. Water consumption, body weight and assessment of overt behavioral signs indicative of a drug withdrawal syndrome were obtained at specific times during the drug-free period. PB-5 rats showed little evidence of withdrawal while PB-20 rats demonstrated the greatest degree of withdrawal. Peak withdrawal scores were observed to be 1, 3.8 and 5 for PB-5, PB-13, and PB-20, respectively. Withdrawal scores for group PB-13 and PB-20 were found to be significantly greater than either control or PB-5 but were not significantly different from each other. Body weight for PB-13 and PB-20 mice declined slightly (nonsignificant) during the drug-free period while a significant decrease (40% decline) in water consumption was demonstrated by 24 hours of this period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intensity of the withdrawal syndrome varies with duration of pentobarbital administration. 262 53


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