Cebranopadol (developmental code GRT-6005) is an

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

of the benzenoid class which is currently under development internationally by

Grünenthal Grünenthal is a pharmaceutical company headquartered in Aachen in Germany. It was founded in 1946 as Chemie Grünenthal and has been continuously family-owned. The company was the first to introduce penicillin into the German market in the po ...

, a

German German(s) may refer to: * Germany (of or related to) **Germania (historical use) * Germans, citizens of Germany, people of German ancestry, or native speakers of the German language ** For citizens of Germany, see also German nationality law **Ger ...

pharmaceutical company The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered to patients (or self-administered), with the aim to cure them, vaccinate them, or alleviate sympto ...

, and its partner

Depomed Assertio Therapeutics, Inc. (formerly Depomed, Inc.) is an American specialty pharmaceutical company. It mainly markets products for treatment in neurology, pain and diseases of the central nervous system. Depomed was founded in 1995 and is headqu ...

, a pharmaceutical company in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

, for the treatment of a variety of different acute and chronic pain states. As of November 2014, it is in phase III

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s. Cebranopadol is unique in its mechanism of action as an opioid, binding to and activating all four of the opioid receptors; it acts as a

full agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical � ...

(K_i = 0.7 nM; EC₅₀ = 1.2 nM; IA = 104%), and

δ-opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous ligan ...

(K_i = 18 nM; EC₅₀ = 110 nM; IA = 105%), and as a

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...

of the nociceptin receptor (K_i = 0.9 nM; EC₅₀ = 13.0 nM; = 89%) and

κ-opioid receptor The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP, is a G protein-coupled receptor that in humans is encoded by the ''OPRK1'' gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind op ...

(K_i = 2.6 nM; EC₅₀ = 17 nM; IA = 67%). The EC₅₀ values of 0.5–5.6 µg/kg when introduced intravenously and 25.1 µg/kg after oral administration. Cebranopadol shows highly potent and effective

antinociceptive Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the Somatosensory system, sensory nervous system's process of encoding Noxious stimulus, noxious stimuli. It deals with a series of events and processes required for an org ...

and

antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests tha ...

effects in a variety of different animal models of pain. Notably, it has also been found to be more potent in models of chronic neuropathic pain than acute

nociceptive pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

compared to selective μ-opioid receptor agonists. Relative to morphine,

tolerance Tolerance or toleration is the state of tolerating, or putting up with, conditionally. Economics, business, and politics * Toleration Party, a historic political party active in Connecticut * Tolerant Systems, the former name of Veritas Software ...

to the analgesic effects of cebranopadol has been found to be delayed (26 days versus 11 days for complete tolerance). In addition, unlike morphine, cebranopadol has not been found to affect

motor coordination Motor coordination is the orchestrated movement of multiple body parts as required to accomplish intended actions, like walking. This coordination is achieved by adjusting kinematic and kinetic parameters associated with each body part involved in t ...

or reduce respiration in animals at doses in or over the dosage range for analgesia. As such, it may have improved and prolonged efficaciousness and greater

tolerability Tolerability refers to the degree to which overt adverse effects of a drug can be tolerated by a patient. Tolerability of a particular drug can be discussed in a general sense, or it can be a quantifiable measurement as part of a clinical study. U ...

in comparison to currently available opioid analgesics. As an agonist of the κ-opioid receptor, cebranopadol may have the capacity to produce psychotomimetic effects, dysphoria, and other

adverse reaction An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...

s at sufficiently high doses, a property which could potentially limit its practical clinical dosage range, but would likely reduce the occurrence of patients taking more than their prescribed dose.

References

External links

Cebranopadol - AdisInsight

Cebranopadol Search Results - ClinicalTrials.gov
{{Opioid receptor modulators Analgesics Opioids Arylcyclohexylamines Indoles Kappa-opioid receptor agonists Mu-opioid receptor agonists Delta-opioid receptor agonists Nociceptin receptor agonists Experimental drugs

See also

References

External links