Characteristics of TRK-130 (Naltalimide), a Novel Opioid Ligand, as a New Therapeutic Agent for Overactive Bladder

@article{Fujimura2014CharacteristicsOT,
  title={Characteristics of TRK-130 (Naltalimide), a Novel Opioid Ligand, as a New Therapeutic Agent for Overactive Bladder},
  author={Morihiro Fujimura and Naoki Izumimoto and Shinobu Momen and Satoru Yoshikawa and Ryosuke Kobayashi and Sayoko Kanie and Mikito Hirakata and Toshikazu Komagata and Satoshi Okanishi and Tadatoshi Hashimoto and Naoki Yoshimura and Koji Kawai},
  journal={The Journal of Pharmacology and Experimental Therapeutics},
  year={2014},
  volume={350},
  pages={543 - 551}
}
We characterized TRK-130 (N-[(5R,6R,14S)-17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxymorphinan-6-yl]phthalimide; naltalimide), an opioid ligand, to clarify the therapeutic potential for overactive bladder (OAB). In radioligand-binding assays with cells expressing human µ-opioid receptors (MORs), δ-opioid receptors (DORs), or κ-opioid receptors (KORs), TRK-130 showed high selectivity for MORs (Ki for MORs, DORs, and KORs = 0.268, 121, and 8.97 nM, respectively). In a functional assay (cAMP… 
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References

SHOWING 1-10 OF 45 REFERENCES

DPI-221 [4-((α-S)-α-((2S,5R)-2,5-Dimethyl-4-(3-fluorobenzyl)-1-piperazinyl)benzyl)-N,N-diethylbenzamide]: A Novel Nonpeptide δ Receptor Agonist Producing Increased Micturition Interval in Normal Rats

A good safety profile for DPI-221 administered orally, with potent efficacy in modifying bladder activity is indicated, and the most crucial safety aspect of δ agonist administration is the incidence of seizure-like convulsions in rodents.

Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition-reflex pathway in the rat.

The results suggest that 5-HT1A receptors at the L6-S1 level of the spinal cord have an important role in the tonic control of the descending limb of the micturition-reflex pathway in the rat.

Effects of TAK-637, a tachykinin receptor antagonist, on the micturition reflex in guinea pigs.

Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist.

The binding of norBUP to opioid and nociceptin/orphanin FQ (ORL1) receptors, and its effects on [(35)S]guanosine-5'-O-(gamma-thio)triphosphate ([(35]S]GTP gamma S) binding mediated by opioid or ORL1 receptors are described and highlighted.

Pharmacological actions of AH-9700 on micturition reflex in anesthetized rats.

Role of dopamine D1 and D2 receptors in the micturition reflex in conscious rats

The results suggest that in conscious rats, D1 receptors tonically inhibit the micturition reflex and that D2 receptors are involved in facilitation of the mitzurition Reflex, which may be speculated that detrusor hyperreflexia associated with Parkinson's disease results from activation failure of D 1 receptors and that administration of D2 receptor agonists might worsen the condition.

Opioid receptor subtypes involved in the central inhibition of urinary bladder motility.

Signal transduction correlates of mu opioid agonist intrinsic efficacy: receptor-stimulated [35S]GTP gamma S binding in mMOR-CHO cells and rat thalamus.

The results suggest that the intrinsic efficacy of agonists at G-protein-coupled receptors is determined primarily by the ability of the agonist-occupied receptor to promote high-affinity GTP binding to the G- protein and to catalytically activate a maximal number G-proteins.

Actions of tramadol on micturition in awake, freely moving rats

(±)‐Tramadol effectively inhibits micturition in conscious rats by stimulating μ‐opioid receptors and a synergy between opioid receptor stimulation and monoamine reuptake inhibition may contribute to the mictURition effects.

Pharmacological evaluation of JO 1870: relation to the potential treatment of urinary bladder incontinence.

Results indicate that JO 1870 is a nonanticholinergic agent that potently increases bladder capacity, likely through an opioid mechanism, and may have potential use in the treatment of urinary incontinence.