Selective κ receptor partial agonist HS666 produces potent antinociception without inducing aversion after i.c.v. administration in mice
It is hypothesized that brain‐penetrant κ receptor ligands possessing biased agonism towards G protein signalling over β‐arrestin2 recruitment would produce robust antinociception with fewer associated liabilities.
Local peripheral antinociceptive effects of 14-O-methyloxymorphone derivatives in inflammatory and neuropathic pain in the rat.
Bone Reinnervation After Fracture: A Study in the Rat
- J. Li, T. Ahmad, M. Spetea, M. Ahmed, A. Kreicbergs
- BiologyJournal of Bone and Mineral Research
- 1 August 2001
The study shows that intense nerve regeneration occurs in early fracture healing partly unrelated to neovascularization, and may prove to be essential for delivery of neuronal mediators required for normal callus formation and/or neov vascularization.
Peripheral versus Central Antinociceptive Actions of 6-Amino Acid-Substituted Derivatives of 14-O-Methyloxymorphone in Acute and Inflammatory Pain in the Rat
The present data indicate that the 6-amino acid conjugates of 14-O-methyloxymorphone have limited access to the central nervous system and can mediate antinociception at peripheral sites and might find clinical application when the central actions of opioids are unwanted.
Modulation of basal and stress‐induced amygdaloid substance P release by the potent and selective NK1 receptor antagonist L‐822429
Self‐regulatory capacity of SP‐mediated neurotransmission that differs in the effect on basal and stress‐induced release of SP is suggested.
Synthesis and biological evaluation of 14-alkoxymorphinans. 22.(1) Influence of the 14-alkoxy group and the substitution in position 5 in 14-alkoxymorphinan-6-ones on in vitro and in vivo activities.
Findings provide further evidence that the nature of the substituent at position 14 has a major impact on the abilities of morphinan-6-one derivatives to interact with opioid receptors.
Discovery and biological evaluation of a diphenethylamine derivative (HS665), a highly potent and selective κ opioid receptor agonist
- M. Spetea, I. Berzetei-Gurske, Elena Guerrieri, J. Mallareddy, G. Tóth, H. Schmidhammer
- Biology, ChemistryBMC Pharmacology and Toxicology
- 1 September 2012
In opioid receptor binding and functional assays, the N-cyclobutylmethyl substituted derivative 4 (HS665) showed the highest affinity and selectivity for the KOP receptor and KOP agonist potency.
Alteration in endogenous opioid systems due to chronic inflammatory pain conditions.
In vitro and in vivo pharmacological profile of the 5-benzyl analogue of 14-methoxymetopon, a novel μ opioid analgesic with reduced propensity to alter motor function
Pharmacological Investigations of N-Substituent Variation in Morphine and Oxymorphone: Opioid Receptor Binding, Signaling and Antinociceptive Activity
The N-phenethyl derivatives of morphine and oxymorphone were very potent in stimulating G protein coupling and intracellular calcium release through the MOP receptor, and were highly effective against acute thermal nociception in mice with marked increased antinociceptive potency compared to the lead molecules.