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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substantial and prolonged withdrawal hyperexcitability in the neural substrate for affective defense was revealed by behavioral and electrophysiological measures in cats exposed to moderate to heavy doses of alcohol for periods ranging from 6 to 72 hours. The data are interpreted as indicating a rapid development of physical dependence on alcohol in this portion of the central nervous system.
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PMID:Hyperexcitability in the neural substrate of emotional behavior in cats after alcohol withdrawal. Evidence of a rapid development of alcohol dependence. 0 May 49

1 Four benzomorphans which have potent antinociceptive activity in the hot-plate and writhing tests in the mouse but do not suppress or precipitate withdrawal symptoms in the morphine-dependent monkey, have been examined for their pharmacological actions in the guinea-pig ileum and mouse vas deferens. 2 In the guinea-pig ileum their agonist potencies are 1.5 to 400 times greater than that of normorphine of morphine whereas in the mouse vas deferens their potencies relative to morphine are 0.3 to 100. They exhibit no antagonist activity in either preparation. Benzomorphans which substitute for morphine in the morphine-dependent monkey do not show such differences between their relative potencies in the guinea-pig ileum and mouse vas diferens. 3 The relative potencies of the four benzomorphans to inhibit stereospecific [3H]-dihydromorphine binding by membrane fragments from rat brain, are more closely related to their relative agonist potencies in the mouse vas deferens than to those found in the guinea-pig ileum. 4 In order to antagonize the agonist actions of these benzomorphans, naloxone is required in concentrations which are 3 to 7 times higher than those needed for the antagonism of normorphine or morphine or of benzomorphans which suppress abstinence in morphine-dependent monkeys. 5 It may be possible to use the three assays, namely, ratio of relative agonist potency in mouse vas deferens to that in guinea-pig ileum, ratio of relative agonist potency to relative affinity to opiate receptors and the concentration of nalozone required for antagonism, for the prediction of the potential of new compounds to produce physical dependence.
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PMID:Assessment in the guinea-pig ileum and mouse vas deferens of benzomorphans which have strong antinociceptive activity but do not substitute for morphine in the dependent monkey. 0 59

Five different strains of mice were investigated for their suitability to serve as models for the study of long-term effects of propoxyphene napsylate (PN) on narcotic-dependent mice. The NIH/Swiss outbred strain proved to be most suitable because of its high liability to manifest physical dependence on morphine. Following removal of subcutaneously-implanted morphine pellets from the mice, the incidence of spontaneous withdrawal jumping was used as a quantifiable criterion of physical dependence. An orally administered suspension of PN suppressed the withdrawal jumping in a dose-dependent manner. However, chronic (daily) administration of PN at doses high enough to prevent withdrawal jumping was characterized by a high degree of toxicity.
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PMID:Model to study long-term effects of propoxyphene napsylate (darvon-N) on narcotic-dependent mice. 0 76

In mice rendered morphine-dependent by pellet implantation for 3 days, the administration of pargyline 6 hours after pellet removal intensified narcotic abstinence behavior, particularly the narcotic withdrawal jumping response. Pargyline, 75 mg/kg i.p., caused a 6- to 9-fold increase in the incidence of jumping in mice withdrawing from morphine 6 hours after removal of the pellet, whereas this effect was not observed: 1) 1 hour after the injection of pargyline or 2) in animals still implanted with the morphine pellet. The median effective dose (ED50) of pargyline required to elicit withdrawal jumping in mice implanted with morphine decreased with increasing physical dependence. The ED50 for 72 hours was about one-sixth that after 24 hours of implantation. Additionally, pargyline potentiated naloxone-precipitated withdrawal jumping as evidenced by a reduction of the naloxone ED50 by approximately one-half. Administration of other monoamine oxidase inhibitors such as pheniprazine, iproiazid or tranylcypromine failed to alter the indicence of jumping in dependent mice undergoind abrupt morphine with drawal. Further, dopamine receptor stimulation by amphetamine, pheniprazine or amantadine antagonized the pargyline-induced jumping response. These data suggest that the increased incidence of withdrawal jumping observed after pargyline in morphine-dependent mice is not related to monoamine oxidase inhibition but rather to a possible pargyline-induced decrease in dopaminergic activity.
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PMID:Precipitation of abstinence-like syndrome in morphine-dependent mice by pargyline. 1 Apr 29

Since an abstinence syndrome may accompany the injection of opioids in addicts pretreated with propranolol the morphine antagonistic properties of this compound were investigated. Racemic propranolol did not significantly affect the antinociceptive ED50 of morphine in rodents and neither precipitated abstinence in morphine-dependent monkeys nor exacerbated the syndrome in 24 hr withdrawn monkeys. Multiple doses of propranolol did not alter the development of physical dependence on morphine in monkeys. Clinical narcotic antagonism would not be predicted from this profile. Evidence for a possible propranolol-morphine interaction came from studies using the mouse tail flick test. Thus, after 8 injections of propranolol (over 4 days) mice were tolerant to normally effective doses of morphine. Concurrent injections of naloxone antagonised this effect. When propranolol and morphine were administered concurrently the morphine ED50 (on day 5) was twice that of the group receiving morphine alone. Similar results were obtained with d-propranolol; practolol had a neutral effect.
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PMID:Effect of propranolol on antinociceptive, tolerance- and dependence-producing properties of morphine in rodents and monkeys. 1 99

Single-dose physical dependence on morphine, as indicated by the mouse withdrawal jumping test, was reduced in a dose-related fashion by co-administration of naloxone. In the same dose range, naloxone also antagonized the antinociceptive effect of morphine in the mouse writhing test. Dose-response data revealed essentially the same ED50's for naloxone in both tests. These results indicate that naloxone does indeed block the development of morphine-induced single-dose physical dependence in mice and that it does so as effectively as it blocks morphine-induced inhibition of writhing.
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PMID:Antagonism by naloxone of morphine-induced single-dose dependence and antinociception in mice. 1 48

alpha-d-Propoxyphene and its principle metabolite, alpha-d-norpropoxyphene, were compared pharmacologically to establish their relative opioid profiles as defined by naloxone reversal. Propoxyphene exhibited opioid activity in the following tests: mouse abdominal constriction and rat tail heat analgesic tests, inhibition of the twitch of the guinea-pig ileum and acute lethality in rodents. Norpropoxyphene also showed opioid activity in the rat tail heat and guinea-pig ileum tests, but exhibited nonopioid activity in the mouse abdominal constriction and acute toxicity studies. Jumping in mice, precipitated by naloxone, suggests the following order for liability to produce physical dependence after repeated administration: morphine greater than codeine greater than propoxyphene greater than norpropoxyphene approximately saline. Propoxyphene and norpropoxyphene depressed axonal conduction in isolated peripheral nerve and were comparable in potency to standard local anesthetic agents. The nonopioid actions of norpropoxyphene might be due in part to its local anesthetic properties.
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PMID:Propoxyphene and norpropoxyphene: pharmacologic and toxic effects in animals. 1

Biochemical and physiological theories of opiate addiction are reviewed in an historical context. The biochemical evidence implicating acetylcholine and norepinephrine in the phenomena of tolerance and physical dependence is described, and the six major biochemical and physiological theories are reviewed, emphasizing their close ties (differing sometimes only linguistically) with late nineteenth century theories of tolerance and physical dependence. The operational-reductionistic approaches taken by these theorists, especially when defining psychic dependence, is criticized from a phenomenological point of view while also emphasizing that characteristics of the social structure and moral viewpoints must also be taken into account when studying these phenomena.
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PMID:Biochemical and physiological approaches to opiate dependence. 1 51

N-Alkyl derivatives of B/C-cis- and B/C-trans-6-hydroxy-1,3,4,9,10,10a-hexahydro-2H-10,4a-methanoimino-ethanophenanthrene have been prepared. The analgesic potency and physical dependence capacity of these compounds were determined. The N-methyl derivatives were analgesically equipotent with morphine. None of these compounds except the N-methyl-B/C-trans isomer 2b suppressed or precipitated the abstinence syndrome. Compound 2b was a narcotic agonist. The N-methyl-B/C-cis compound 2a appears to warrant further examination for its potential as a potent analgesic having no physical dependence liability.
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PMID:B/C-cis- and -trans-1,3,4,9,10,10a-Hexahydro-2H-10,4a-methanoiminoethanophenanthrene (homo- and homoisomorphinan) derivatives as analgesics. 1 53

Disputing the concept of "psychic dependence", the authors review six motivations to use addictive drugs, four of which pertain to the moment of assumption of the habit, and two of which, identifiable with physical and psychic dependence, depend on breaking of the habit. While physical dependence is linked to withdrawal syndrome, psychic dependence, in the authors' opinion, is related to a longstanding previous state of true of masked endogenous depression (in this case it would be well termed "neuropsychological dependence"), and the drug taking is only a maladaptive self-medication. This thesis is substantiated by the literature reporting, in chronic drug addicts, the use of the whole series of antidepressants (i.e. tricyclics, doxepine, lithium, etc.) with noticeable therapeutical success. In accordance with other reports and with personal experience, the authors assign great importance to the drugs acting, directly or indirectly, on GABA, i.e. L-glutamine, piracetam, and, particularly, N-dipropylacetic acid.
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PMID:Psychic dependence? A different formulation of the problem with a view to the reorientation of therapy for chronic drug addiction. 2 89


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