New Opioid Ligands May Provide Pain Relief Without Addiction Risk

PainRelief.com Interview with:

Prof. Dr. Christoph Stein Direktor Institut für Experimentelle Anaesthesiologie Charité Campus Benjamin Franklin Freie Universität Berlin 

Prof. Stein

Prof. Dr. Christoph Stein
Direktor
Institut für Experimentelle Anaesthesiologie
Charité Campus Benjamin Franklin
Freie Universität Berlin 

PainRelief.com: What is the background for this study? What are the main findings? 

Response: Our group has studied the biology and pharmacology of opioid receptors on peripheral sensory neurons (i.e. outside the central or intestinal nervous system) for over 25 years. We have always aimed at finding mechanisms and opioid receptor ligands that can be developed into drugs inhibiting pain without eliciting typical adverse effects of conventional opioids such as apnoea, addiction, sedation or constipation.

From our previous work we knew that the selective activation of opioid receptors on peripheral sensory neurons can produce powerful pain relief in animals and human patients. Those analgesic effects are particularly strong in pain caused by tissue injury and inflammation (e.g. postoperative pain, arthritis). Together with mathematicians (Dr. Marcus Weber) at the Zuse Institute Berlin, we started out with computer simulations examining the interaction between opioid ligands and receptors in normal (noninflamed) and inflamed environments. These studies indicated a stronger binding of conventional opioid ligands (morphine, fentanyl) to opioid receptors at increased proton concentrations (i.e. low pH, as present in acidotic/inflamed tissue). We also knew that the protonation of a tertiary amine in the ligand is required for opioid receptor activation. Using those in silico simulations, we now designed a new ligand (NFEPP) that is only protonated (and capable of activating opioid receptors) at low pH, but not at normal pH (as in brain and intestinal wall). After synthesis of NFEPP (and similar derivatives) by a contractor we tested them in vitro and in vivo. NFEPP produced opioid receptor activation and analgesia selectively at low pH/tissue inflammation (as present in nerve injury/neuropathy and abdominal inflammation) without eliciting respiratory depression, addiction potential, sedation or constipation. 

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New Technique Can Help Pinpoint Where Heroin Batches Come From

New method describes measuring  strontium isotopes can be used as a chemical marker for geography and geology to differentiate heroin samples from different geographic regions.

Joshua DeBord, Ali Pourmand, Sarah C. Jantzi, Sini Panicker, Jose Almirall. Profiling of heroin and assignment of provenance by 87 Sr/ 86 Sr isotope ratio analysis. Inorganica Chimica Acta, 2017; DOI: 10.1016/j.ica.2017.07.049

FDA To Require Opioid Manufacturers To Train Health Care Providers

The FDA “notified 74 manufacturers of immediate-release opioid analgesics intended for use in the outpatient setting that their drugs will now be subject to a more stringent set of requirements under a Risk Evaluation and Mitigation Strategy (REMS).

The REMS requires that training be made available to health care providers who prescribe IR opioids, including training on safe prescribing practices and consideration of non-opioid alternatives.”

FDA Takes Important Steps to Stem the Tide of Opioid Misuse and Abuse

Emergency Rooms Using Shorter, Lower Doses of Opioids

A recent study from the Annals of Emergency Medicine founds that compared to other settings, emergency room prescriptions for opioids found more likely to be in compliance with CDC recommendations and have a lower risk of progression to long term opioid use.

CVS To Limit Opioid Prescriptions To 7 Days For New Patients

As part of CVS’s commitment to fighting the national opioid abuse epidemic, CVS is:

  •  limiting to seven days the supply of opioids dispensed for certain acute prescriptions for patients who are new to therapy;
  • limiting the daily dosage of opioids dispensed based on the strength of the opioid; and
  • requiring the use of immediate-release formulations of opioids before extended-release opioids are dispensed.

https://cvshealth.com/newsroom/press-releases/cvs-health-fighting-national-opioid-abuse-epidemic-with-enterprise-initiatives

Hard Questions To Ask Yourself and Your Doctor About Opioids for Pain Relief

The American Society of Anesthesiologists suggests you ask yourself and your physician some tough questions about pain medications, whether related to surgery or not.

Some of the questions are straightforward including:

WHY WAS I PRESCRIBED OPIOIDS?

ARE THERE OTHER PAIN MANAGEMENT OPTIONS?

Download this informative brochure from the American Society of Anesthesiologists