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)

1. The effects of the benzodiazepine receptor antagonists Ro 15-1788 (flumazenil) and the beta-carboline ZK 93426 were compared in dogs before and after chronic treatment with diazepam. 2. In diazepam-naive dogs, the most prominent behavioural alterations occurring during or after i.v. infusion of Ro 15-1788 up to a dose of 20 mg kg-1 were transient sedation, ataxia, and 'hot foot' behaviour, whereas behavioural alterations observed after ZK 93426 were not different from those observed after i.v. infusion of vehicle alone. This indicates that, in contrast to Ro 15-1788, ZK 93426 did not exert partial agonistic activity at benzodiazepine receptors. 3. In dogs treated 3 times daily with diazepam, 1 mg kg -1 orally, for 1 week, both benzodiazepine antagonists precipitated abstinence symptoms but the number and severity of withdrawal signs induced by Ro 15-1788 were greater than with ZK 93426. 4. In dogs treated 3 times daily with diazepam, 2 mg kg-1 orally, for 2 weeks, severe abstinence symptoms were precipitated in all animals by infusion of either antagonist but differences were found in the type of the symptoms: Ro 15-1788 induced rigid postures or rigid walking with increased muscle tone, tremor, twitches and jerks, whereas ZK 93426 did not alter motility but induced generalized myoclonic jerks and tonic-clonic seizures. A generalized tonic-clonic seizure was also observed in one dog of the trial with infusion of Ro 15-1788. 5. Plasma level determinations during chronic treatment diazepam showed marked accumulation of the major active metabolite desmethyldiazepam, whereas diazepam levels were at least 15 times lower, which might suggest that desmethyldiazepam was responsible for the development of physical dependence on diazepam.
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PMID:Physical dependence on diazepam in the dog: precipitation of different abstinence syndromes by the benzodiazepine receptor antagonists Ro 15-1788 and ZK 93426. 256 47

Young chimpanzees (Pan troglodytes) will accept ethanol in quantities sufficient to produce symptoms of withdrawal when ethanol is subsequently discontinued. Mild to severe symptoms of physical dependence, including grand mal seizures, are observed when ethanol is abruptly withdrawn after 6 to 10 weeks of chronic oral intake. In addition, the rate of disappearance of ethanol in blood increased during periods of chronic ingestion, an indication of developing metabolic tolerance. These results suggest that the young chimpanzee may be a suitable model for experimental studies of alcoholism.
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PMID:The chimpanzee as an animal model for investigating alcoholism. 506 36