Synthesis of 7β-hydroxy-8-ketone opioid derivatives with antagonist activity at mu- and delta-opioid receptors

Ahonen, Tiina Johanna; Rinne, Maiju; Grutschreiber, Peter; Mätlik, Kert; Airavaara, Mikko; Schaarschmidt, Dieter; Lang, Heinrich; Reiss, David J; Xhaard, Henri; Gavériaux‐Ruff, Claire; Yli‐Kauhaluoma, Jari; Moreira, Vânia M.

doi:10.1016/j.ejmech.2018.02.074

Cited by 4 publications

(4 citation statements)

References 57 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…G protein-coupled receptors (GPCRs) are signalling proteins activated by for example neurotransmitters and neuromodulators and as such are involved in many physiological processes. Their location as a cellular gateway makes them key targets for drug discovery and chemical biology 1–3 , and 30–50% of drugs on the market have been reported to target GPCRs directly or indirectly 4 .…”

Section: Introductionmentioning

confidence: 99%

Cartography of rhodopsin-like G protein-coupled receptors across vertebrate genomes

Rinne

Tanoli

Khan

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

We conduct a cartography of rhodopsin-like non-olfactory G protein-coupled receptors in the Ensembl database. The most recent genomic data (releases 90–92, 90 vertebrate genomes) are analyzed through the online interface and receptors mapped on phylogenetic guide trees that were constructed based on a set of ~14.000 amino acid sequences. This snapshot of genomic data suggest vertebrate genomes to harbour 142 clades of GPCRs without human orthologues. Among those, 69 have not to our knowledge been mentioned or studied previously in the literature, of which 28 are distant from existing receptors and likely new orphans. These newly identified receptors are candidates for more focused evolutionary studies such as chromosomal mapping as well for in-depth pharmacological characterization. Interestingly, we also show that 37 of the 72 human orphan (or recently deorphanized) receptors included in this study cluster into nineteen closely related groups, which implies that there are less ligands to be identified than previously anticipated. Altogether, this work has significant implications when discussing nomenclature issues for GPCRs.

show abstract

Section: Introductionmentioning

confidence: 99%

Cartography of rhodopsin-like G protein-coupled receptors across vertebrate genomes

Rinne

Tanoli

Khan

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…The main opioid receptors are the μ-opioid receptor (μOR), κ-opioid receptor (κOR), δ-opioid receptor (δOR), and nociception/orphanin FQ peptide receptor. All of them belong to the superfamily of G-protein coupled receptors (GPCRs), which is one of the largest family of receptors, , sharing about 70% sequence identity . Opioids are capable of binding to these receptors and triggering several secondary responses inside the cell.…”

Section: Pharmacology Of Desomorphinementioning

confidence: 99%

“…All of them belong to the superfamily of G-protein coupled receptors (GPCRs), which is one of the largest family of receptors, 42,43 sharing about 70% sequence identity. 44 Opioids are capable of binding to these receptors and triggering several secondary responses inside the cell. As consequence, opioid action is responsible for the inhibition of the presynaptic release of several neurotransmitters such as GABA, noradrenaline, and acetylcholine.…”

Section: ■ Pharmacology Of Desomorphinementioning

confidence: 99%

DARK Classics in Chemical Neuroscience: Krokodil

Alves

2020

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Krokodil is the street name for a homemade mixture that has been used as a cheap substitute for heroin. The main active substance in krokodil is desomorphine, an opioid that is 10 times more potent than morphine. Krokodil use began in Russia and Ukraine but has spread throughout several countries in Europe and North America. Krokodil is produced from codeine tablets in a bootleg reaction performed under clandestine and unsanitary conditions. The toxicity of krokodil is characterized by devastating symptoms that start as black ulcers at the injection site and evolve to gangrene and limb amputation. The dangerous effects of krokodil are associated with its homemade nature and lack of purification prior to use. In this review, we discuss the chemical and pharmacological properties and the metabolism of desomorphine, the preparation of krokodil, and how its homemade nature contributes to its toxicity. The synthesis of krokodil produces several other morphinans in addition to desomorphine that warrant further study as possible analgesic alternatives to morphine.

show abstract

“…Sus efectos están mediados principalmente por el receptor opioide mu (MOR, por sus siglas en inglés). Este tiene dos tipos de receptores altamente relacionados: delta (DOR, por sus siglas en inglés) y kappa (KOR, por sus siglas en inglés) [53].…”

Section: Expresión En Sistemas Biológicosunclassified

Quimiogenómica y Quimiogenética: Definiciones, técnicas y aplicaciones en el ámbito farmacéutico

Arroyo-Rodríguez¹,

González-Young²,

Hernández-Vega³

et al. 2020

View full text Add to dashboard Cite

En los años 80, tomó fuerza la ciencia dirigida al estudio del genoma humano, cuyo objetivo era mejorar la salud humana a través de la identificación de genes. Este estudio permitió el surgimiento de ciencias, entre ellas la Quimiogenómica y la Quimiogenética. La Quimiogenómica es un área interdisciplinaria que busca la sistematización del genoma al identificar, analizar, expandir y predecir las interacciones de los ligandos con las proteínas por medio de métodos in vitro e in silico. Por otro lado, la Quimiogenética se refiere al estudio de las características genéticas de un paciente para optimizar la Farmacoterapia y predecir la eficacia, los efectos secundarios y la dosificación de fármacos selectos. El conocimiento de las interacciones entre moléculas y proteínas específicas ayudaron al desarrollo de nuevas herramientas biotecnológicas y a la identificación de novedosas dianas farmacológicas que pudieran conducir a conocimientos más específicos. Algunas aplicaciones en estudio en el ámbito farmacéutico son los receptores diseñados exclusivamente activados por fármacos diseñados (DREADDs, por sus siglas en inglés). Con ellos se pretende que no se activen ante ligandos endógenos, sino en presencia de sintéticos. Actualmente existen muchas investigaciones en los cuales se estudian DREADDs para la identificación de neuronas y de vías de señalización involucradas en patologías como el miedo, la ansiedad, la depresión, la adicción y la obesidad.

show abstract

Synthesis of 7β-hydroxy-8-ketone opioid derivatives with antagonist activity at mu- and delta-opioid receptors

Cited by 4 publications

References 57 publications

Cartography of rhodopsin-like G protein-coupled receptors across vertebrate genomes

Cartography of rhodopsin-like G protein-coupled receptors across vertebrate genomes

DARK Classics in Chemical Neuroscience: Krokodil

Quimiogenómica y Quimiogenética: Definiciones, técnicas y aplicaciones en el ámbito farmacéutico

Contact Info

Product

Resources

About