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)

According to the hypothesis that the development of physical dependence on and tolerance to opiates depends on the inhibition by opiates of L-asparaginase and L-glutaminase activities in the brain, and the blockade by opiates of the aspartatergic/glutamatergic receptors especially NMDA, four female and fourty-four male heroin addicts were included in a double-blind clinical trial. Four mg chlorpromazine (CPZ) was administered every hour and 10 mg diazepam (DIA) every 6 hours to a group consisting of two female and nineteen male inpatients. The remaining subjects received 15 mg non-opioid antitussive dextromethorphan (DM) instead of CPZ. The withdrawn addicts were controlled twice a day and yawning, lacrimation, rhinorrhoea, perspiration, goose flesh, muscle tremor, dilated pupils, anorexia, joint and muscle aches, restlessness, insomnia, emesis, diarrhea, craving and rejection of smoking as abstinence syndrome signs were observed and rated on a scale of 1, 2 and 3 points according to their intensity. All signs, except perspiration and emesis, were significantly less intense in the group given DM + DIA than CPZ + DIA. The other plus points included the immediate stop of craving and the early onset of smoking in DM + DIA group. The results are considered to be supporting evidence for the hypothesis emphasizing the blockade of NMDA receptors by opiates in opiate addiction. Furthermore, the decrease caused by non-opioid NMDA antagonists in the responsiveness of NMDA receptors appears very promising for the treatment of opiate addicts.
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PMID:The treatment of heroin addicts with dextromethorphan: a double-blind comparison of dextromethorphan with chlorpromazine. 218 2

A classical approach to the control of food consumption has been to assume separate mechanisms for the arousal to eat, on the one hand, and the satiation of feeding responses, on the other. The present paper is concerned with a single, and a comparatively simple, neuronal mechanism which is endowed with properties to allow the complete determination of the level of feeding, from hyperphagia to anorexia. The model for the control of feeding, which is presented here, draws attention to the benzodiazepine receptor found distributed through the brain, and present in certain hypothalamic nuclei. Recent evidence which characterizes the receptor is reviewed, and the various categories of benzodiazepine receptor ligands are described. Pharmacological data, collected in a palatable food consumption model using non-food-deprived rats, demonstrate that benzodiazepine receptor agonists produce hyperphagia, benzodiazepine receptor inverse agonists produce anorexia, and benzodiazepine receptor antagonists block both effects. Hence, bidirectional control of food intake can be achieved through differential ligand action at a common set of receptors. Speculatively, these data can be extended, if it is assumed that two endogenous ligands exist in the brain which act like benzodiazepine agonist and inverse agonist, respectively. Evidence for the presence in hypothalamic nuclei of endogenous ligands of the latter kind is discussed. Benzodiazepine withdrawal-induced anorexia is also described, and is taken as evidence for the part played by feeding mechanisms in the development of benzodiazepine physical dependence.
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PMID:Bidirectional control of palatable food consumption through a common benzodiazepine receptor: theory and evidence. 286 20

Sprague-Dawley male rats were intoxicated with morphine, using an ingestion method where exposed and control rats received equivalent amounts of calories and nutrients. The degree of physical dependence on morphine was demonstrated by studying and quantifying abstinence symptoms after withdrawal or after administration of opiate antagonists. The aims of the study were (1) to further enlighten the specificity and validity of the intoxication method concerning physical dependence, and (2) to determine whether some of the abstinence signs might be of value to facilitate quantitation of the degree of physical dependence on morphine, with diet and fluid intake being maintained under control. Withdrawn rats showed a decreased fluid diet intake and a body weight loss, the latter partly due to anorexia. Other mild abstinence signs were irritation, tremor and some motor excitation. The body weight loss during the first day of morphine withdrawal was proportional to the accumulated drug dose (between 25 and 300 mg morphine PO/kg b.wt.). However, prolonged morphine treatment on one dose (340 mg/kg b.wt.) did not reinforce the body weight changes caused by morphine withdrawal. The succeeding weight gain some days after morphine withdrawal was not entirely dependent on the amount of fluid diet intake. Methadone was shown to partially block the decrease in diet intake and the weight loss seen during morphine withdrawal. The naloxone-precipitated withdrawal symptoms were motor excitation, cholinergic signs, body weight loss, diarrhoea and decreased diet intake. The weight loss 2 hr after naloxone administration to long-term intoxicated rats was proportional to the naloxone dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aspects of abstinence after morphine ingestion. 365 10

Dogs were treated with clonazepam, 0.5 mg/kg orally, b.i.d., for 3-6 weeks. The development of tolerance to the anticonvulsant effect was followed by weekly determinations of the convulsive threshold by infusion of pentetrazole, 10 min after i.v. injection of 0.1 mg/kg clonazepam. In all 6 dogs tolerance was apparent after 1-2 weeks of treatment; in 1 dog the anticonvulsant effect had been totally lost after 3 weeks of treatment. Tolerance is regarded to be "functional" since the elimination half-life of clonazepam increased considerably with the duration of the treatment. One day after withdrawal of clonazepam the convulsive threshold had fallen below the control value in all dogs, but 1 week later it had recovered to the control level. Other signs of physical dependence after withdrawal were hyperthermia in 2 dogs as well as anorexia with weight loss in 5 out of the 6 dogs. In anesthetized dogs, relaxed by suxamethonium and ventilated, the effect of repeated injections of clonazepam on the EEG spiking activity maintained by an infusion of pentetrazole was studied; there was no indication for the development of acute tolerance.
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PMID:Anticonvulsant effect of clonazepam in the dog: development of tolerance and physical dependence. 409 13

We relate two cases of amineptine (Survector) overconsumption by patients cured for atypical depression with asthenia and activities deficit as the prevalent symptoms. Prescription of two tablets a day (0,200 g) was respected in one case during six months, and in the other case during two years, with therapeutic benefit on apragmatism. To no obvious reason, within few months both patients had gradually raised the doses to twenty tablets (2 g) and thirty tablets (3 g) respectively: we observed subexcitation, insomnia, sensorial hyperaesthesia, irritability, tachyphemia with dysarthria, anorexia with weight lost of more than 10 kg and amphetamine-like troubles without confusion or delusion, as a result of which both patients were treated for their addiction, in hospital. Treatment with clorazepate perfusions did not cause any physical dependence problems. However, psychological dependence was strong enough for one of the patients to go out, on the third day, against medical decision. As far as we know, in France, only one such case of addiction use at high doses and in single intakes is mentioned in the existing literature. However, our observations suggest that it might be necessary to re-assess the place of amineptine among new antidepressive molecules with psychostimulant abilities.
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PMID:[2 cases of amineptine dependence]. 614 28

This research was designed to determine whether the convulsion-eliciting action of tranylcypromine (TCP) during bartibal (B) withdrawal was specific to physical dependence on B, and to compare the findings with the action of pentetrazol (PTZ). Challenge with 15-20 mg/kg IP TCP at 48 or B withdrawal resulted in the elicitation of clonic-tonic convulsion (CTC) in all rats (n = 6) within 10 min. Another challenge with 5-20 mg/kg TCP led to the dose-related precipitation and intensification of CTC. The CTC-inducing action of TCP was relatively reduced as the B withdrawal signs were gradually mitigated. In other words, when challenge with the drug was made at 72h of B withdrawal, the time of CTC onset was prolonged, and the incidence was reduced to 50% in parallel with abolition of the other withdrawal signs. A challenge at 120 h of B withdrawal when the vital signs had almost recovered to prewithdrawal level failed to induce even the prodromal signs of convulsion. In all rats exhibiting only mild to moderate withdrawal signs (such as hyperirritability, hyper-reflexia, anorexia, weight loss), 40 mg/kg TCP was required to induce CTC during B withdrawal, which was twice the dose required in severely dependent rats. Other monoamine oxidase inhibitors, i.e., pargyline, iproniazid, and clorgyline, elicited no CTC during B withdrawal. Methamphetamine was without effect on B withdrawal convulsions. From these findings, the convulsive threshold for TCP during B withdrawal proved well correlated to the grade of B-dependence and the duration of B-withdrawal signs.
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PMID:Specific action of tranylcypromine to precipitate barbital withdrawal convulsions. 681 26