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)

To observe the dispositional and functional tolerance to and physical dependence on barbital, the influence of repeated administration of the drug on serum barbital levels, coordinative motion, body weight, and cortical evoked potential was assessed. Rats administered the first dose of barbital showed marked impairment of gross behavior and then loss of the righting reflex. While they were repeatedly treated with barbital for a 4-week period, the CNS depression became weaker and weaker, and loss of the righting reflex was no longer observed. Serum barbital levels after administration of barbital tended to decrease by the 28th day of repeated drug administration. Coordinative motion was markedly impaired after administration of the first dose, but gradually recovered during the repeated administration period. Barbital at 100 mg/kg, i.p., prolonged the latent time of the evoked potential in normal untreated rats but not in tolerant rats. During the withdrawal period, no particular change was observed in the animals' gross behavior. However, body weight loss and shortening of the latent time of the evoked potential were observed at 60 to 72 hours of withdrawal. These results suggest that cortical evoked potential can serve as a useful method for observing tolerance to and physical dependence on barbital.
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PMID:Observation of the development of tolerance to and physical dependence on barbital by cortical evoked potential in rats. 188 Sep 88

We studied the involvement of beta-adrenoceptors in the physical dependence formation of barbital. 1. Propranolol (at a dose of 0.5 or 1.0 mg/g food) and barbital were applied simultaneously as a mixture with animal food (barbital-propranolol combination). Barbital was applied on a schedule of gradually increasing dosages from 0.5-and-1.0 to 6-and-8 mg/g food over 36 days. Only the animals dosed with barbital exhibited severe withdrawal signs such as spontaneous withdrawal convulsions. The animals dosed with propranolol alone showed no changes even on withdrawal of the drug. The formation of physical dependence on barbital was obviously inhibited by the combination of barbital and propranolol. 2. Cross-application of propranolol (30 and 60 mg/kg, p.o., and 10 and 30 mg/kg, i.p.) following withdrawal of barbital resulted in the inhibition of the spontaneous withdrawal convulsions, muscle rigidity and hyperirritability. It also inhibited significantly tranylcypromine-induced convulsions, while it failed to inhibit similarly induced hyperthermia. These results including previous findings of effects of monoamine-related compounds on barbital withdrawal convulsions suggest that the balance of activities of noradrenergic neurons, especially that of alpha- and beta- receptors, has great influence on both the formation of physical dependence on barbital and the manifestation of withdrawal convulsions.
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PMID:Effects of propranolol on barbital dependence formation and withdrawal signs. 668 67

Rats were rendered physically dependent on phenobarbital by phenobarbital-admixed foods. Barbital, phenobarbital, ethanol, diazepam, nitrazepam, meprobamate, methaqualone, chlorpromazine, diphenylhydantoin, mephenesin, reserpine and clonidine were cross-administered to evaluate the mode of suppression of withdrawal signs and cross-physical dependence liability. The drugs were administered several times during the period from 17-18 hr (when withdrawal signs began to appear) to about 48 hr after the withdrawal of phenobarbital. From the mode of suppression and severity of relapsed withdrawal signs, these drugs were classified into the following 3 types: Type 1: drugs suppressing withdrawal signs of phenobarbital (WSP) almost completely and followed by the relapse of severe WSP. Type II-a: drugs suppressing WSP partially and followed by the relapse of moderate WSP. Type II-b: drugs suppressing WSP partially and followed by the relapse of only mild or practically no signs. Type III (III-a and -b): drugs practically failing to suppress or rather aggravate WSP. Consequently, we found that it was possible to evaluate precisely the cross-physical dependence on sedative-hypnotics by means of investigation for the method of suppression of WSP and the relapse of such signs upon their withdrawal.
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PMID:Cross-physical dependence liability of psychotropic drugs in rats dependent on barbiturates. 668 5