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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2008-8-19
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pubmed:abstractText |
H(2)N-Tyr-D-Thr-Gly-Phe-Leu-Ser-(O-beta-D-lactose)-CONH(2) (MMP2200) is a novel glycopeptide opioid agonist with similar affinities for mu and delta receptors. Glycosylation promoted brain penetration and production of centrally mediated behavioral effects in mice; however, it is unknown whether the magnitude of enhanced brain penetration is sufficient to permit central mediation of drug effects and production of synergistic mu/delta antinociceptive interactions after systemic administration in primates. To address this issue, the present study compared the effects of MMP2200 and the mu-agonist morphine in four behavioral procedures in rhesus monkeys. In an assay of thermal nociception, morphine (1.0-5.6 mg/kg) produced dose-dependent antinociception, whereas MMP2200 (10-56 mg/kg) was ineffective. In an assay of capsaicin-induced thermal allodynia, both morphine (0.01-1.0 mg/kg) and MMP2200 (0.032-3.2 mg/kg) produced dose-dependent antiallodynic effects. MMP2200-induced antiallodynia was blocked by the moderately mu-selective antagonist naltrexone (0.01 mg/kg), the delta-selective antagonist naltrindole (1.0 mg/kg), and the peripherally selective opioid antagonist quaternary naltrexone (0.32 mg/kg). In an assay of schedule-controlled behavior, both morphine (0.01-1.0 mg/kg) and MMP2200 (10-56 mg/kg) decreased response rates. Morphine effects were antagonized by naltrexone (0.001-0.01 mg/kg); however, the effects of MMP2200 were not antagonized by either naltrexone (0.01 mg/kg) or naltrindole (1.0 mg/kg). In an assay of drug self-administration, morphine (0.0032-0.32 mg/kg/injection) produced reinforcing effects, whereas MMP2200 (0.032-0.32 mg/kg/injection) did not. These results suggest that systemically administered MMP2200 acted as a peripheral, mu/delta-opioid agonist with limited distribution to the central nervous system in rhesus monkeys. These results also suggest the existence of species differences in the pharmacokinetics and brain penetration of glycopeptides.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-10891118,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-11181927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-11714884,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-12065726,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-12373443,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-12829725,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-12966560,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-14557380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-15152028,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-15155552,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-15166257,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-15194208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-15792997,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-16019946,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-16751796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-17313456,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-1760731,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-17619998,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-2465635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-2539460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-2548877,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-2566676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-3713205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-569699,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-6262493,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-6716270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-7901396,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-8246165,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-8371142,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-8396630,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-9580592,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-9655854,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18511649-9655881
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1521-0103
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
326
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
939-48
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pubmed:dateRevised |
2011-5-24
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pubmed:meshHeading |
pubmed-meshheading:18511649-Analgesics, Opioid,
pubmed-meshheading:18511649-Animals,
pubmed-meshheading:18511649-Behavior, Animal,
pubmed-meshheading:18511649-Dose-Response Relationship, Drug,
pubmed-meshheading:18511649-Female,
pubmed-meshheading:18511649-Glycopeptides,
pubmed-meshheading:18511649-Macaca mulatta,
pubmed-meshheading:18511649-Male,
pubmed-meshheading:18511649-Opioid Peptides,
pubmed-meshheading:18511649-Pain Measurement,
pubmed-meshheading:18511649-Receptors, Opioid, delta,
pubmed-meshheading:18511649-Receptors, Opioid, mu
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pubmed:year |
2008
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pubmed:articleTitle |
Behavioral pharmacology of the mu/delta opioid glycopeptide MMP2200 in rhesus monkeys.
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pubmed:affiliation |
Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
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