Identification of Opioid Ligands Possessing Mixed μ Agonist/δ Antagonist Activity among Pyridomorphinans Derived from Naloxone, Oxymorphone, and Hydromorphone.

Ananthan, Subramaniam; Khare, Naveen K.; Saini, Surendra Kumar; Seitz, Lainne E.; Bartlett, Jeffrey L.; Davis, Peg; Dersch, Christina M.; Porreca, Frank; Rothman, Richard B.; Bilsky, Edward J.

doi:10.1021/jm0400597

Cited by 17 publications

(34 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, recent studies carried out with rats have shown that oxymorphone does not affect sperm count, motility or reproductive organ weights in males (81). The latter finding may be due to a compensatory effect of DOR and MOR, since oxymorphone displays almost equal binding affinity at both receptors (82).…”

Section: Regulation Of Sperm Fertility By the Opioid Systemmentioning

confidence: 93%

Regulation of Male Fertility by the Opioid System

Subirán

Casis

Irazusta

2011

Mol Med

View full text Add to dashboard Cite

Section: Regulation Of Sperm Fertility By the Opioid Systemmentioning

confidence: 93%

Regulation of Male Fertility by the Opioid System

Subirán

Casis

Irazusta

2011

Mol Med

View full text Add to dashboard Cite

“…Nonpeptide m-Opioid Receptor Agonist/d-Opioid Receptor Antagonists. The hydroxymorphinan-derived pyridomorphinan SoRI 20411 [59-(4-Chlorophenyl)-6,7-didehydro-4,5a-epoxy-3-hydroxy-17-methylpyrido [29,39: 6,7]morphinan] is a MOPr agonist/DOPr antagonist with approximately 10-fold lower antinociceptive potency than morphine (intracerebroventricular administration) and with low propensity to produce analgesic tolerance (Ananthan et al, 2004). Compared with the latter compound, the 14-alkoxypyridomorphinan SoRI 22138 [59-(4-Chlorophenyl)-17-(cyclopropylmethyl)-6,7-didehydro-4,5a-epoxy-3-hydroxy-14-(3-phenylpropoxy)pyrido [29,39:6,7]morphinan] is a more potent and more balanced MOPr agonist/DOPr antagonist (Ananthan et al, 2012) (Fig.…”

Section: Mixed M-opioid Receptor Agonists/d-opioid Receptor Antagomentioning

confidence: 99%

Molecular Pharmacology ofδ-Opioid Receptors

et al. 2016

View full text Add to dashboard Cite

“…In conformity with the expectations, this mixed agonist/ ␦ antagonist ligand did not produce any signifi cant tolerance on repeated administration. 62 Compounds possessing ␦ antagonist and weak agonist activity have been found in other C-ring annulated morphinans such as the pyrrolomorphinans. Among a limited number of such pyrrolomorphinans synthesized and evaluated, it was found that compound 16 possessing a 4-methylphenyl substituent on the pyrrole ring displayed ␦ antagonist activity with a K e of 14.1 nM and partial agonist activity with and EC 50 of 1360 nM and E max of 34% in [ 35 S]GTP ␥ S binding assays in CHO cells expressing human ␦ and opioid receptors.…”

Section: E122mentioning

confidence: 99%

Opioid ligands with mixed μ/δ opioid receptor interactions: An emerging approach to novel analgesics

Ananthan

2006

AAPS J

Self Cite

126

110

View full text Add to dashboard Cite

A BSTRACTOpioids are widely used in the treatment of severe pain. The clinical use of the opioids is limited by serious side effects such as respiratory depression, constipation, development of tolerance, and physical dependence and addiction liabilities. Most of the currently available opioid analgesics exert their analgesic and adverse effects primarily through the opioid receptors. A large number of biochemical and pharmacological studies and studies using genetically modifi ed animals have provided convincing evidence regarding the existence of modulatory interactions between opioid and ␦ receptors. Several studies indicate that ␦ receptor agonists as well as ␦ receptor antagonists can provide benefi cial modulation to the pharmacological effects of agonists. For example, ␦ agonists can enhance the analgesic potency and effi cacy of agonists, and ␦ antagonists can prevent or diminish the development of tolerance and physical dependence by agonists. On the basis of these observations, the development of new opioid ligands possessing mixed agonist/ ␦ agonist profi le and mixed agonist/ ␦ antagonist profi le has emerged as a promising new approach to analgesic drug development. A brief overview of -␦ interactions and recent developments in identifi cation of ligands possessing mixed agonist/ ␦ agonist and agonist/ ␦ antagonist activities is provided in this report. K EYWORDS:Analgesics , Opioid Ligands , Mixed Mu/Delta agonists , Mixed Mu agonist/Delta antagonists , Peptides , Nonpeptides INTRODUCTIONOpioid analgesics are the standard therapeutic agents for the treatment of moderate-to-severe pain. These drugs exert their analgesic activity through their interaction with the opioid , ␦ , or receptors as agonists. The clinical usefulness of opioid agonists such as morphine, however, is limited by signifi cant side effects such as respiratory depression, constipation, development of tolerance and physical dependence, and addiction potential. One approach to limit -receptor-mediated side effects is to selectively target ␦ and opioid receptors. This approach has been explored using agonist ligands selective for ␦ and opioid receptors but has seen only limited success. The ␦ agonists generally display limited analgesic effi cacy and receptor agonists are limited to their use as peripheral analgesics owing to their psychotomimetic and dysphoric central effects. An alternative approach that is gaining considerable interest is the development of compounds that possess mixed opioid activity at the different opioid receptors. 1 , 2 Several lines of evidence indicate the existence of physical and functional interactions between the opioid receptors, particularly between the and ␦ receptors. Several biochemical and pharmacological studies using and ␦ receptor ligands gave an early indication of such interactions between the and ␦ receptors. [3][4][5][6] The and ␦ opioid receptors exist on overlapping populations of neurons in painmodulating regions of the central nervous system, and the presence of both and ␦ receptors ...

show abstract

Identification of Opioid Ligands Possessing Mixed μ Agonist/δ Antagonist Activity among Pyridomorphinans Derived from Naloxone, Oxymorphone, and Hydromorphone.

Cited by 17 publications

References 0 publications

Regulation of Male Fertility by the Opioid System

Regulation of Male Fertility by the Opioid System

Molecular Pharmacology ofδ-Opioid Receptors

Opioid ligands with mixed μ/δ opioid receptor interactions: An emerging approach to novel analgesics

Contact Info

Product

Resources

About