New mu-opioid receptor agonists with phenoxyacetic acid moiety.

نویسندگان

  • Susumu Sato
  • Teruo Komoto
  • Yoshihiko Kanamaru
  • Noriyuki Kawamoto
  • Tomomi Okada
  • Terumitsu Kaiho
  • Kinichi Mogi
  • Shinichi Morimoto
  • Norimitsu Umehara
  • Tadayuki Koda
  • Akira Miyashita
  • Takao Sakamoto
  • Yasuhiro Niino
  • Tetsuo Oka
چکیده

New muq-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, 12-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest agonist potency on the MOR in an isolated guinea-pig ileum preparation, and it also had selectivity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells compared with the same types of delta- and kappa-opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more potent MOR agonist activity than loperamide. Furthermore, compound 8 showed a peripheral analgesic activity in vivo screening on rat.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

New mu-opioid receptor agonists with piperazine moiety.

New mu-opioid receptor (MOR) agonists containing piperazine and homopiperazine moieties in the structures were synthesized and their affinities to and agonist potencies on MOR were evaluated. Among the synthesized compounds, 4-[4-(2-methoxyphenyl)piperazin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide (20 Aa) showed the highest affinity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 c...

متن کامل

Involvement of Mu Opioid Receptor Signaling in The Protective Effect of Opioid against 6-Hydroxydopamine-Induced SH-SY5Y Human Neuroblastoma Cells Apoptosis

Introduction: The neuroprotective role of opioid morphine against 6-hydroxydopamineinduced cell death has been demonstrated. However, the exact mechanism(s) underlying such neuroprotection, especially the role of subtype receptors, has not yet been fully clarified. Methods: Here, we investigated the effects of different opioid agonists on 6-OHDA-induced neurotoxicity in human neuroblastoma...

متن کامل

Mu Opioid Receptor Gene: New Point Mutations in Opioid Addicts

Introduction: Association between single-nucleotide polymorphisms (SNPs) in mu opioid receptor gene and drug addiction has been shown in various studies. Here, we have evaluated the existence of polymorphisms in exon 3 of this gene in Iranian population and investigated the possible association between these mutations and opioid addiction.  Methods: 79 opioid-dependent subjects (55 males, 24...

متن کامل

Ligand-selective activation of mu-oid receptor: demonstrated with deletion and single amino acid mutations of third intracellular loop domain.

The mechanism for the differential regulation of the mu-opioid receptor by agonists is investigated by identifying the receptor domains used to define the relative efficacies of three mu-opioid receptor-selective agonists: [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), morphine, and [N-MePhe3,D-Pro4]-morphiceptin (PL017) to inhibit forskolin-stimulated intracellular cAMP production in human emb...

متن کامل

Presynaptic mu-opioid receptors regulate a late step of the secretory process in rat ventral tegmental area GABAergic neurons.

Gamma-aminobutyric acid (GABA)-containing interneurons of the ventral tegmental area (VTA) regulate the activity of dopaminergic neurons. These GABAergic interneurons are known to be innervated by synaptic terminals containing enkephalin, an endogenous ligand of mu-opioid receptors. Bath application of mu-opioid receptor agonists inhibits the activity of VTA GABAergic neurons but the mechanism ...

متن کامل

ذخیره در منابع من

ذخیره در منابع من قبلا به منابع من ذحیره شده

{@ msg_add @}


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Chemical & pharmaceutical bulletin

دوره 50 2  شماره 

صفحات  -

تاریخ انتشار 2002