Curr Top Med Chem. 2007;7(4):363-73.

Kappa receptor bivalent ligands.

Source

Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, Massachusetts 02478, USA.

Abstract

Bivalent ligands of kappa opioid agonists and antagonists, such as norBNI and BNI, are used as tools to elucidate the kappa receptor characteristics. Bivalent ligands may also be effective analgesics although none have this far been used clinically. Structure-activity relationships (SAR) and molecular modeling led to the development of a more potent and selective kappa antagonist (5'-guanidinylnaltrindole, GNTI). Novel homo and hetero bivalent ligands with high mixed kappa/micro or mixed kappa/delta affinity and intriguing pharmacological properties may eventually lead to useful analgesics with fewer adverse side effects. Bivalent ligands were also developed that could act as probes of the receptor-oligomerzation and organization phenomena. A structurally unique kappa antagonist (JDTic) provides an additional tool to characterize kappa opioid receptor.

PMID:: 17305578; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

R0-1-DA14251/DA/NIDA NIH HHS/United States

LinkOut - more resources

Full Text Sources

Other Literature Sources

COS Scholar Universe

Molecular Biology Databases

NALTREXONE - HSDB

Supplemental Content

Icon for Bentham Science Publishers Ltd.

Save items

Related citations in PubMed

Binding of norbinaltorphimine (norBNI) congeners to wild-type and mutant mu and kappa opioid receptors: molecular recognition loci for the pharmacophore and address components of kappa antagonists. [J Med Chem. 2000]
Binding of norbinaltorphimine (norBNI) congeners to wild-type and mutant mu and kappa opioid receptors: molecular recognition loci for the pharmacophore and address components of kappa antagonists.
Larson DL, Jones RM, Hjorth SA, Schwartz TW, Portoghese PS. J Med Chem. 2000 Apr 20; 43(8):1573-6.
Potent and selective indolomorphinan antagonists of the kappa-opioid receptor. [J Med Chem. 2000]
Potent and selective indolomorphinan antagonists of the kappa-opioid receptor.
Stevens WC Jr, Jones RM, Subramanian G, Metzger TG, Ferguson DM, Portoghese PS. J Med Chem. 2000 Jul 13; 43(14):2759-69.
Opioid antagonist activity of naltrexone-derived bivalent ligands: importance of a properly oriented molecular scaffold to guide "address" recognition at kappa opioid receptors. [J Med Chem. 1996]
Opioid antagonist activity of naltrexone-derived bivalent ligands: importance of a properly oriented molecular scaffold to guide "address" recognition at kappa opioid receptors.
Bolognesi ML, Ojala WH, Gleason WB, Griffin JF, Farouz-Grant F, Larson DL, Takemori AE, Portoghese PS. J Med Chem. 1996 Apr 26; 39(9):1816-22.
Review Selective naltrexone-derived opioid receptor antagonists. [Annu Rev Pharmacol Toxicol. 1992]
Review Selective naltrexone-derived opioid receptor antagonists.
Takemori AE, Portoghese PS. Annu Rev Pharmacol Toxicol. 1992; 32:239-69.
Review Conformation-activity relationships of opioid peptides with selective activities at opioid receptors. [Biopolymers. 1999]
Review Conformation-activity relationships of opioid peptides with selective activities at opioid receptors.
Hruby VJ, Agnes RS. Biopolymers. 1999; 51(6):391-410.

See reviews... See all...

Cited by 4 PubMed Central articles

Opioid bifunctional ligands from morphine and the opioid pharmacophore Dmt-Tic. [Eur J Med Chem. 2011]
Opioid bifunctional ligands from morphine and the opioid pharmacophore Dmt-Tic.
Balboni G, Salvadori S, Marczak ED, Knapp BI, Bidlack JM, Lazarus LH, Peng X, Si YG, Neumeyer JL. Eur J Med Chem. 2011 Feb; 46(2):799-803. Epub 2010 Dec 8.
Synthesis and biological evaluation of bivalent ligands for the cannabinoid 1 receptor. [J Med Chem. 2010]
Synthesis and biological evaluation of bivalent ligands for the cannabinoid 1 receptor.
Zhang Y, Gilliam A, Maitra R, Damaj MI, Tajuba JM, Seltzman HH, Thomas BF. J Med Chem. 2010 Oct 14; 53(19):7048-60.
Synthesis and opioid receptor binding affinities of 2-substituted and 3-aminomorphinans: ligands for mu, kappa, and delta opioid receptors. [J Med Chem. 2010]
Synthesis and opioid receptor binding affinities of 2-substituted and 3-aminomorphinans: ligands for mu, kappa, and delta opioid receptors.
Decker M, Si YG, Knapp BI, Bidlack JM, Neumeyer JL. J Med Chem. 2010 Jan 14; 53(1):402-18.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Kappa receptor bivalent ligands.
Kappa receptor bivalent ligands.
Curr Top Med Chem. 2007 ;7(4):363-73.

PubMed
Epitope peptides and immunotherapy.
Epitope peptides and immunotherapy.
Curr Protein Pept Sci. 2007 Feb ;8(1):109-18.

PubMed
Nonconscious activation of behavioral goals, a methodologically refined replicat...
Nonconscious activation of behavioral goals, a methodologically refined replication.
Psychol Rep. 2006 Dec ;99(3):963-70.

PubMed
Food consumption and cancer of the colon and rectum in north-eastern Italy.
Food consumption and cancer of the colon and rectum in north-eastern Italy.
Int J Cancer. 1992 Jan 21 ;50(2):223-9.

PubMed
Fungal biodegradation of carbofuran and carbofuran phenol by the fungus Mucor ra...
Fungal biodegradation of carbofuran and carbofuran phenol by the fungus Mucor ramannianus: identification of metabolites.
Water Sci Technol. 2007 ;55(1-2):163-7.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: