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)

2,4,5-Trimethylpyrrole-3-carboxylic acid esters of tropanols and related monocyclic amino alcohols were synthesized and evaluated for analgesic activity by the mouse hot-plate and Nilsen methods. 1-Methyl-4-piperidinol 4-(2,4,5-trimethylpyrrole-3-carboxylate) (7) exhibited activity in the morphine--codeine range (mouse hot plate). In monkeys, 7 acted neither as a typical narcotic agonist nor as a typical antagonist and it showed no physical dependence liability of the morphine-type. Whereas the pethidine and prodine analgesics have quaternary phenyl substituion at C-4 of the piperidine ring, compound 7 does not.
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PMID:Pyrrole esters of tropanols and related structures as analgesics. 40 88

To ascertain roles of the two basic nitrogen atoms in 1-substituted 4-[2,(3-hydroxyphenyl)-1-phenylethyl]-piperazine derivatives (1) in the expression of opioid agonist and antagonist activities, a methine group (CH) was isosterically substituted for nitrogen atom at the 1-position (N-1) in compound 1 to obtain 4-substituted 1-[2-(3-hydroxyphenyl)-1-phenylethyl]piperidine derivatives (2). Their analgesic action and ability to produce physical dependence (jump-producing activity) as the mu-opioid receptor specific in vivo actions, and narcotic antagonist action in mice were compared with those of compound 1. Results of this study showed that, in cases of the racemate and the (S)-(+) enantiomer, opioid agonist activities (analgesic and jump-producing activities) were not greatly affected by the methine-substitution for N-1 in compound 1, but that the narcotic antagonist activity of the (R)-(-) enatiomer was abolished by this substitution. It thus appears that N-1 in compound 1 contributes to the expression of narcotic antagonist activity, whereas the nitrogen atom at the 4-position corresponds to the tyramine moiety necessary for the expression of mu-opioid agonist activity.
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PMID:Roles of two basic nitrogen atoms in 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives in production of opioid agonist and antagonist activities. 1074 22