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)

We have previously demonstrated the antagonizing effect of aspartic acid on some effects of morphine and on the development of physical dependence on, and tolerance to, morphine. In the present study, we have withdrawal from morphine or administration of a morphine antagonist. For this purpose sixty five white rats were given morphine and aspartic acid separately and in combination in a 5% saccharose solution instead of drinking water for 30 days. Some of the dependent rats were then withdrawn and others were injected with levallorphan. Flying, jumping, wet-dog shaking, body weight loss and motor activity were estimated and free amino acid levels in the brain were determined. Aspartic acid was found to prevent or antagonize the behavioural signs and the changes in the free amino acid levels in the brain. The results are discussed in the light of the previous data.
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PMID:The antagonizing effect of aspartic acid on morphine withdrawal and levallorphan-precipitated abstinence syndrome signs and on associated changes in brain levels of free amino acids in the rat. 10 53

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

As free amino acids in the brain have a role in the development of physical dependence on and tolerance to morphine, and in the mechanism of action of some drugs, the effects of aspartic acid which antagonizes some effects of the single dose of morphine were studied during the development of the physical dependence on morphine and after the withdrawal of morphine. 108 rats were given morphine and aspartic acid in different combinations in drinking water for 30 days. Every tenth day the dose of morphine was increased: At the end of this period some of them in each group continued or began to receive aspartic acid depending on the experimental conditions after the withdrawal of morphine. During the experiments body weight, spontaneous motor activity and analgesic threshold were determined. Aspartic acid prevented the alterations induced by morphine during the development of physical dependence and tolerance. Furthermore the rats that received aspartic acid after the withdrawal showed no body weight loss.
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PMID:Antagonizing effect of aspartic acid on the development of physical dependence on and tolerance to morphine in the rat. 57 36

It has previously been shown that subchronic and acute administration of L-asparaginase and glutaminase inhibitors D-Aspartic acid (D-ASP) and prolyl-leucyl-glycinamide (PLG) intensifies and attenuates morphine (M) physical dependence, respectively, by the inhibition of ASP and glutamic acid (GLU) production, and subsequently their normal releases. Tizanidine (TIZ) has long been known to be an alpha 2-adrenoceptor agonist and inhibitor of ASP and GLU release. Therefore, in this study TIZ has been administered subchronically during the development of M physical dependence to rats in which M-containing pellets had been implanted or acutely 30 min before naloxone (NL)-induced abstinence syndrome. The subchronic administration of TIZ intensified NL-precipitated abstinence syndrome whereas its acute administration attenuated it, as did D-ASP and PLG. On the other hand, TIZ added into the medium prevented the in vitro M-dependent-made guinea pig ileum from contracting following NL application. Furthermore, TIZ stopped the already started contraction by NL of the M-dependent ileum, which completely relaxed later. These effects of TIZ on M-dependent ileum were antagonized by the alpha 2-adrenoceptor antagonist yohimbine. The intensification by subchronic TIZ administration of abstinence syndrome was attributed to the lesser release of ASP and GLU, which resulted in the larger blockade of M of ASPergic/GLUergic receptors due to the lesser release of their endogenous agonist ASP and GLU and consequently the higher upregulation of the receptors. The attenuation by acute TIZ administration of NL-precipitated abstinence syndrome was explained with lesser release of ASP and GLU and concomitantly the lesser stimulation of the receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of tizanidine on morphine physical dependence: attenuation and intensification. 135 95

The partial agonist at benzodiazepine receptors, Ro 19-8022, has been characterized as a putative anxiolytic drug with an improved side effect profile. This orally active compound is a representative of a quinolizinone structure class and shows potent anticonflict activity in mice and rats. It protects rodents from convulsions induced by pentylenetetrazol, N-methyl-D-aspartic acid and maximal electroshock, as well as against audiogenic seizures, with an efficacy comparable to that of the full agonist alprazolam. No appreciable sedative or motor-impairing effects could be detected up to a very high dose (100 mg/kg) in the horizontal wire test or the rotarod performance test in mice and rats and in spontaneous behavior in monkeys. Consistent with its characterization as a partial agonist, Ro 19-8022 antagonized the motor impairment induced by the full agonists diazepam or meclonazepam measured in horizontal wire and rotarod tests in rodents, and reduced flunitrazepam-induced effects in squirrel monkeys, with an efficacy comparable to that of the benzodiazepine receptor antagonist flumazenil. After subchronic administration of Ro 19-8022 to mice, antagonist-precipitated withdrawal syndrome was dramatically weaker than after alprazolam treatment, which is indicative of a lower physical dependence liability of Ro 19-8022. Pharmacodynamic effects recorded in convulsion and reversal of motor impairment tests after i.v. administration suggest a long duration of action of this compound. Taken together, such preclinical data suggest that benzodiazepine receptor partial agonists with a neurological and behavioral profile such as that of Ro 19-8022 may offer an innovative therapeutic approach to the treatment of anxiety disorders.
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PMID:Ro 19-8022, a nonbenzodiazepine partial agonist at benzodiazepine receptors: neuropharmacological profile of a potential anxiolytic. 135 50

The inhibition by opiates and the sudden normalization by opioid antagonists of the brain L-asparaginase activity (BAA) have previously been reported to be the main factors in the development of physical dependence and the manifestation of precipitated abstinence syndrome, respectively. As a result, L-asparaginase inhibitors D-aspartic acid and prolyl-leucyl-glycinamide (PLG) were separately given to mice and rats either just after morphine (M)-containing pellet implantation or 15 min before naloxone (NL)-precipitated abstinence syndrome. The animals treated in this manner were used to assess the intensity of the physical dependence and to determine the BAA. D-ASP or PLG administration following pellet implantation significantly increased all of the observed signs such as flying, jumping, wet dog shake and writhing. When D-ASP or PLG were given 15 min before precipitated abstinence they significantly decreased the number of the signs. The determination of the BAA showed significant decreases or increases more or less parallel to the severity of the physical dependence on M. The intensification of physical dependence by D-ASP or PLG given just after the pellet implantation was attributed to their additional inhibitory effect to that of M on the BAA at the beginning of the physical dependence development. The attenuating effect of BAA inhibitors D-ASP or PLG administered before precipitated abstinence was explained with the prevention of the increase in the BAA.
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PMID:Intensification and attenuation of morphine dependence by D-aspartic acid and PLG. 196 65

The activities of the brain L-asparaginase and angiotensin converting enzyme (ACE), and the plasma cortisol level were found to be decreased in the rats implanted with morphine (M) containing pellets. Even though 10 mg/kg of naloxone (N) itself showed an inhibitory effect on ACE it abolished the inhibitions seen in the M dependent rats five min following subcutaneous injection. The chronic administration of L-aspartic acid (ASP) during the development of physical dependence or just before the N injection prevented the increase of the plasma cortisol caused by N. It is concluded that in addition to the inhibition of the brain L-asparaginase activity which was previously hypothesized to be the main reason of the development of physical dependence on opiates as a result of the related experimental and clinical data, the inhibition by M of the brain ACE activity may take part in the development of physical dependence. With regard to the plasma cortisol level, the concomitant administration of ASP with M blocks, to a great extent, the development of physical dependence on opiate. The single dose of ASP administration before N injection prevents the effect of N, the manifestation of abstinence syndrome.
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PMID:Brain asparaginase, ACE activity and plasma cortisol level in morphine dependent rats: effect of aspartic acid and naloxone. 302 85

According to the hypothesis implying that the main reason of physical dependence on opiate is the inhibition of brain L-asparaginase activity and L-aspartic acid gradually decreases compulsory opiate intake so that physical dependence disappears by itself, 31 opiate addicts were given 8 g L-aspartic acid for 7 days after withdrawal from opiate and appearance of abstinence syndrome signs. The attenuations by L-aspartic acid of the abstinence syndrome signs were statistically compared with those obtained from other 12 opiate addicts received daily 50 mg chlorpromazine + 60 mg diazepam which have long been used to suppress abstinence syndrome because of their multiple receptor blocking and sedative effects. The intensity and duration of 13 signs out of 16 ones were found to be significantly more alleviated and shortened in the addicts treated with L-aspartic acid.
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PMID:Comparison of the suppressive effects of L-aspartic acid and chlorpromazine + diazepam treatments on opiate abstinence syndrome signs in men. 381 27

Chronic administration of ethanol in animals leads to CNS tolerance and physical dependence. Subsequent withdrawal of ethanol causes hyperexcitability which is thought to be related to increased sensitivity of N-methyl-D-aspartic acid (NMDA) receptors. The purpose of this study was to investigate sensitivity to NMDA in ethanol-treated animals by detecting damage after intrahippocampal injection of NMDA. Choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD) specific activity was used as markers of cholinergic and gamma-aminobutyric acid neurons, respectively. Ethanol-dependent animals were more liable to die following intrahippocampal injection of either 120 or 240 nmol of NMDA. There was a significantly greater decrease in hippocampal GAD but not ChAT specific activity in the surviving animals. These data support the hypothesis that ethanol dependence is associated with increased sensitivity to NMDA which may be responsible for excitotoxic brain damage and death.
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PMID:Increased sensitivity of the hippocampus in ethanol-dependent rats to toxic effect of N-methyl-D-aspartic acid in vivo. 846 3