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)

Abstinence symptoms of doses acutely equi-effective on motocoordination of brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine, We 941, Lendormin) and diazepam in rhesus monkeys were evaluated in a primary dependence study of 61 days. After termination of oral treatment with 3 X 5.4 mg/kg/d brotizolam and 3 X 13.5 mg/kg/d diazepam the duration of withdrawal symptoms varied. Most symptoms of brotizolam abstinence disappeared within 24 h of withdrawal, while the withdrawal symptoms following diazepam were more pronounced between the second and fifth day after termination of administration. Regularly during the whole study, determinations of the serum levels of brotizolam and diazepam were performed. Two days after termination of brotizolam treatment the substance could scarcely be detected in the serum. Diazepam serum levels, in contrast, declined more slowly. The physical dependence capacity of lower daily doses of brotizolam, 3 X 0.2, 3 X 0.6, and 3 X 1.8 mg/kg/d was tested in experiments with chronic administration for 4 weeks. 3 X 1.8 mg/kg/d was the lowest oral dose inducing physical dependence. Taking into consideration the great difference in human therapeutic single dosages, brotizolam is thought to have a very low physical dependence capacity in man, compared with diazepam.
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PMID:Physical dependence capacity of brotizolam in rhesus monkeys. 1st communication: primary dependence studies. 371 83

The degree of physical dependence induced by oral administration of brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine, We 941, Lendormin), triazolam, diazepam and nitrazepam in rhesus monkeys was evaluated in primary dependence studies. Substitution tests were performed in barbital-dependent animals. In the primary dependence studies, two dosages of each compound were administered for four weeks to compare the effects on motocoordination and development of body weight as well as the withdrawal symptoms after interruption of these chronic administrations. Taking into account the therapeutically effective doses in man, brotizolam and triazolam were tested at doses of 2 X 2 and 2 X 3 mg/kg/d. For comparison, 2 X 10 and 2 X 15 mg/kg/d of diazepam and nitrazepam were administered. Brotizolam and triazolam had a shorter duration of action than diazepam and nitrazepam. During chronic administration of brotizolam, triazolam and diazepam all animals gained body weight. Motocoordination was impaired by these compounds to a comparable degree. Nitrazepam, in contrast, was less compatible. It induced a decrease in body weight and a more pronounced disturbance of motocoordination. Only triazolam evoked effects indicating development of tolerance. Compared with the reference compounds, brotizolam induced the weakest degree of physical dependence. In the substitution tests about 2 mg/kg brotizolam, 0.6 mg/kg triazolam, 4.5 mg/kg diazepam and doses of less than 1 mg/kg nitrazepam were equipotent, suppressing withdrawal symptoms of barbital. These results demonstrate that relatively high doses of brotizolam were necessary to substitute barbital. The data obtained in rhesus monkeys are compared with the therapeutic doses in humans and discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Physical dependence capacity of brotizolam in rhesus monkeys. 2nd communication: primary dependence and barbital substitution. 371 84