Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2,4,5-Trimethylpyrrole-3-carboxylic acid esters of tropanols and related monocyclic amino alcohols were synthesized and evaluated for analgesic activity by the mouse hot-plate and Nilsen methods. 1-Methyl-4-piperidinol 4-(2,4,5-trimethylpyrrole-3-carboxylate) (7) exhibited activity in the morphine--codeine range (mouse hot plate). In monkeys, 7 acted neither as a typical narcotic agonist nor as a typical antagonist and it showed no physical dependence liability of the morphine-type. Whereas the pethidine and prodine analgesics have quaternary phenyl substituion at C-4 of the piperidine ring, compound 7 does not.
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PMID:Pyrrole esters of tropanols and related structures as analgesics. 40 88

1. Buprenorphine is a highly lipophilic derivative of oripavine. In rodent antinociceptive assays (writhing, tail pressure), buprenorphine had an action which was rapid in onset and of long duration; it was 25-40 times more potent than morphine after parenteral injection and 7-10 times more potent after oral administration. 2. The log dose-response relationship for buprenorphine was curvilinear in mouse and rat tail flick tests with the antinociceptive effect decreasing at higher, non-toxic doses. 3. Tolerance developed to the antinociceptive activity of buprenorphine in mice. 4. No signs of abstinence were observed on naloxone challenge or after abrupt withdrawal in monkeys receiving buprenorphine chronically for one month. 5. Buprenorphine antagonized the antinociceptive actions of morphine in mouse and rat tail flick tests but was an ineffective antagonist in the rat tail pressure test. 6. Buprenorphine precipitated signs of abstinence in morphine-dependent mice and monkeys but not in morphine-dependent rats. 7. Buprenorphine produced Straub tails in mice. This effect was not antagonized when the animals were pretreated with naloxone. However, in the rat tail pressure test high doses of diprenorphine antagonized established antinociceptive effects of buprenorphine. 8. It is concluded that buprenorphine represents a definite advance in the search for a narcotic antagonist analgesic of low physical dependence potential.
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PMID:Agonist and antagonist properties of buprenorphine, a new antinociceptive agent. 40 48

Since it has been shown in previous study that aspartic acid prevents the development of physical dependence on and tolerance to morphine and antagonizes the abstinence syndrom signs, the biochemical bases of that prevention were investigated in the present study. The brain contents of serotonin, DA, NA, and free amino acids of the rats given aspartic acid and morphine separately and in combination were determined. It has been observed that most of the morphine-induced changes in the brain were normalized in the group given aspartic acid and morphine together. The relative ineffectiveness of aspartic acid in normalizing some amino acid levels decreased by morphine was discussed and some logical explanations were found.
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PMID:The antagonizing effect of aspartic acid on the brain levels of monoamines and free amino acids during the development of tolerance to the physical dependence on morphine. 41 14

The effects of acute and chronic administration of phencyclidine (PCP) were examined in five male squirrel monkeys trained to respond on a chain fixed-interval fixed-ratio schedule of food presentation. Acute PCP (0.01-0.60) mg/kg i.m.) produced dose-related decreases in response rate during both components of the schedule. Both components were equally affected by the drug. The effects of the drug on fixed-interval response rate were dependent on the control rate of responding in corresponding segments of the interval. After the initial dose-response determination, the subjects were placed on an individualized regimen of chronic PCP administration lasting from 82 to 126 days, beginning with daily injections for 2 days alternating with saline injections for 2 days, progressing to four injections daily. No evidence of physical dependence was seen upon withdrawal of the drug. Redetermination of the dose-response function for PCP (0.03-1.0 mg/kg i.m.) demonstrated a nearly 2-fold shift to the right of both the fixed-interval and fixed-ratio dose-response curves, indicating tolerance. In addition, the subjects' behavior recovered sooner from a dose of PCP (0.60 mg/kg i.m.) given after the chronic regimen than from the same dose given before the chronic regimen. The results demonstrate that tolerance can occur to the behavioral effects of PCP in the squirrel monkey.
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PMID:The effects of acute and chronic phencyclidine on schedule-controlled behavior in the squirrel monkey. 41 49

dl-Erythro-1-phenyl-2-(o-chlorophenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl] ethanol dihydrochloride showed orally a definite analgesic activity, without producing the significant morphine-like physical dependence liability, and its analgesic potency was about a half that of codeine and far superior to aminopyrine in experimental animals.
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PMID:Pharmacological studies of a new analgesic, dl-erythro-1-phenyl-2-(o-chlorophenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl] ethanol dihydrochloride, in experimental animals. 44 20

A current practice among drug abusers in certain Midwestern and Eastern cities is the intravenous injection of aqueous mixtures prepared from tablets of pentazocine and tripelennamine. Patients present with acute hypoxic episodes and symptoms suggesting physical dependence to pentazocine. Two cases are presented illustrating acute respiratory distress with hypoxia. Available evidence indicates that the respiratory syndrome is produced by talc from the injected tablets. Respiratory support and short-term oxygen therapy have been effective in managing this syndrome. Approaches to the treatment of pentazocine dependence and the role of the antihistamine in potentiating the narcotic activity are also discussed. Physicians, drug abuse counselors, and others should be aware of the abuse potential and pulmonary damage which can result from the intravenous use of this drug combination.
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PMID:Abuse and pulmonary complications of injecting pentazocine and tripelennamine tablets. 45 20

Rats implanted with a single morphine pellet for a short period of 72 h have been shown to have a lower concentration of enkephalin in the brain, as determined by a radioimmunoassay (RIA) detecting Leu- and Met-enkephalin as well as another endogenous substance. Two other paradigms of morphine implantations did not cause any change in enkephalin levels. Various protocols of morphine injections failed to elicit changes in enkephalin content in the rat brain. The significant decrease observed after the short regimen implantation suggests that at a certain stage in the development of physical dependence a reduction in the amount of enkephalin occurs, but returns to normal values within a short period.
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PMID:Enkephalin levels in rat brain after various regimens of morphine administration. 46 Jul 27

The effect of morphine on the uptake of 45Ca++ was studied in lysed synaptosomes obtained from homogenates of whole mouse brain. The addition of morphine, 10(-6) M, to the incubation medium or acute administration of 10 or 20 mg/kg s.c. resulted in a decrease in 45Ca++ uptake; this decrease was observed only in the presence of ATP (3 mM). In contrast, after morphine pellet implantation (72 hr) to induce tolerance and physical dependence, an enhancement of lysed synaptosomal 45Ca++ uptake occurred; the increase was obtained in the presence but not in the absence of ATP. The enhancement of Ca++ uptake appears to be related with the degree of tolerance and dependence development since a linear relationship was noted between the time of morphine pellet implantation and the increase in 45Ca++ uptake by lysed synaptosomes. The acute inhibitory action on 45Ca++ uptake by morphine was prevented in vitro by naloxone, 1.9 x 10(-8) M, and in vivo by 2 mg/kg of naloxone s.c. and the chronic enhancing action of morphine by the simultaneous implantation of a naloxone pellet with the morphine pellet. The present findings lend further support to our previous reports in which we suggest that alterations in Ca++ flux may be involved with morphine analgesia, tolerance and physical dependence.
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PMID:Effect of morphine on calcium uptake by lysed synaptosomes. 50 67

The homeostat hypothesis of drug addiction states that tolerance and physical dependence may both represent adaptive processes, the body's responses to drugs that change the internal milieu. This conceptual framework inextricably links physical dependence with functional tolerance. Dependence may arise by multiple mechanisms, so that different signs, such as body temperature or CNS excitability, may show different degrees of dependence or may have different time courses. Tolerance may be similarly diverse. It is difficult to test whether tolerance and dependence have the same time course because it is hard to find exactly equivalent signs for such a test. The discrepant data from different laboratories on the rate of recovery from physical dependence may be due to the use of different withdrawal signs as indices. Dissociation of tolerance and dependence has been reported in mice treated with 6-hydroxydopamine, where dependence develops without evidence of tolerance. Conversely, tolerance without expression of dependence is seen in experiments on membranes and synapses in vitro. Changes in lipid composition of cell membranes may explain some kinds of tolerance.
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PMID:Physical dependence on ethanol: its relation to tolerance. 51 Jan 74

The common perception about the individual with quadriplegia (having a lesion at C5 and above) as a fragile, immobile, and medically unstable individual is in direct conflict with the concept of successful rehabilitation. Long hospitalizations, constant medical attention, and profound physical dependence often work against the efforts of those providing rehabilitation to ease the patient's transition back to as normal a life style as possible. This paper describes a successfully executed sensory and motor stimulation program, designed to meet the needs of the sensory-deprived individual with quadriplegia and to deemphasize the perception of both physical and psychological fragility.
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PMID:Increasing sensory and motor stimulation for the patient with quadriplegia. 51 89


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