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Query: UMLS:C0278080 (
physical dependence
)
1,658
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Pro-Leu-Gly-NH2 (
MIF
) and several structural analogues, all injected in 50-microgram doses daily in mice receiving morphine chronically, were found to prevent development of
physical dependence
as measured by changes in body temperature associated with naloxone-induced withdrawal. Dose-response studies, using again a protocol of daily injections of peptide at 50, 5, 0.5, 0.05, 0.005 microgram per mouse revealed
MIF
and cyclo(Leu-Gly) to be the most potent peptides and to be effective in blocking
physical dependence
to morphine at a dose as low as 0.5 and 0.05 microgram per mouse, respectively. The benzyloxycarbonyl derivative of
MIF
, Pro-Leu, and Pro- -Leu exhibited significant activities down to a dose of 5 microgram of peptide per mouse.
...
PMID:Prolyl-leucyl-glycinamide, cyclo(leucylglycine), and derivatives block development of physical dependence on morphine in mice. 28 70
Administration of Pro-Leu-Gly-NH2 (
MIF
) and cyclo (Leu-Gly) blocked the development of tolerance to and
physical dependence
on morphine, induced by the pellet implanation procedure in mice. Inhibition of tolerance development by peptides was evidenced by the presence of an analgesic response (increase in jump threshold) as determined by measuring the jump threshold to an increasing electric current, after a challenge dose of morphine (40 mg/kg). The same dose of morphine did not alter the jump threshold in morphine tolerant mice which were injected with saline prior to pellet implantation. The inhibition of the development of
physical dependence
on morphine by these peptides was evidenced by the antagonism of the hypothermic response which occurs during abrupt or naloxone-induced withdrawal. The naloxone-induced withdrawal jumping response was unaffected by these peptides. Dose-response experiments indicated that cyclo (leu-Gly) was much more potent than
MIF
in these tests. These peptides, when given after the development of tolerance and dependence, did not modify either the analgesic response to morphine or the symptoms of abrupt and naloxone-precipitated withdrawal. The inhibition of development of analgesic tolerance and
physical dependence
was not associated with changes in brain morphine concentration. The data indicate that these peptides do not interfere withe the morphine-morphine receptor complex formation but alter a subsequent step in the genesis of some aspects of tolerance and dependence processes.
...
PMID:Development of narcotic tolerance and physical dependence: effects of Pro-Leu-Gly-NH2 and cyclo (Leu-Gly). 610 69
We have previously shown that
MIF
and its structural analog, cyclo-(Leu-Gly), block analgesic tolerance and some signs of
physical dependence
following chronic opiate administration. The mechanism of action of these peptides has not been clearly elucidated. The data presented here suggests that chronic opiate administration causes a behavioral supersensitivity to dopamine (DA) agonists which is highly correlated with an increase in D2-Hi receptor affinity for DA agonists, but not antagonists. Both the behavioral and receptor changes are blocked by prior administration of cyclo(Leu-Gly). This suggests that the ability of cyclo(Leu-Gly) to block the development of opiate addictive states may involve DA synaptic elements.
...
PMID:Cyclo(Leu-Gly) attenuates the striatal dopaminergic supersensitivity induced by chronic morphine: agonist binding to D2 dopamine receptors correlates with stereotypic behavior. 622 78
