Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of 1-chclohexyl-4-[2-(3-hydroxyphenyl)-1-phenylethyl]piperazine (I) and its 1-(3-methyl-2-butenyl) derivative (II), the S(+)-isomers were analgesically more active than either their +(-)-isomers or their racemates, having 15 to 44 times the potency of morphine in mice and rats. R(-)-I had comparable analgesic activity to morphine R(-)-II to pentazocine in mice, rats and dogs and they were nearly equipotent with pentazocine in reversing some actions of morphine. The S(+)-isomers and racemates lacked this action. R(-)-II required about 10 times more naloxone to reverse its analgesic activity than was needed to antagonise the S(+)-isomers, morphine and pentazocine. The S(+)-isomers and racemates produce a typical Straub tail reaction and increased spontaneous locomotor activity in mice, but the R(-)-isomers did not. R(-)-II had no significant physical dependence liability in mice, rats and monkeys. From these results, it is suggested that the compounds show an uncommon steroselectivity in comparison with morphine and its surrogates, and that R(-)-II is worth investigating further as a narcotic antagonist analgesic.
 ...
PMID:Analgesic and other pharmacological activities of a new narcotic antagonist analgesic (-)-1-(3-methyl-2-butenyl)-4-[2-(3-hydroxyphenyl)-1-phenylethyl]-piperazine and its enantiomorph in experimental animals. 610 65

3-(3-methyl-3-butenyl)-1,2,3,4,5,6-hexahydro-6, 11-dimethyl-8-hydroxy-2,6-methano-3-benzazocine (KF-1820) is a derivative of benzomorphan and is different from pentazocine only in the site of the double bond. KF-1820 showed potent analgesic activity in all tests performed. KF-1820 was 6 to 12 times and 30 to 40 times more potent than morphine and pentazocine, respectively, when administered subcutaneously. KF-1820 had little or no narcotic antagonist property. Physical dependence liability tests indicated that KF-1820 may be a little less, or as liable as, pentazocine to produce physical dependence. ID50 values of KF-1820, pentazocine and morphine for depression of contractions of isolated guinea pig ileum to coaxial stimulation correlated well with their analgesic activities in the rodent. The dissociation equilibrium constant of KP-1820 confirmed the in vivo finding that KF-1820 had little or no narcotic antagonist property.
 ...
PMID:Pharmacological studies of 3-(3-methyl-3-butenyl)-1,2,3,4,5,6-hexahydro-6,11-dimethyl-8-hydroxy-2,6-methano-3-benzazocine. 645 8