Dinalbuphine sebacate (DNS), also known as nalbuphine sebacate or as sebacoyl dinalbuphine ester (SDE) and sold under the brand name Naldebain, is a non-controlled

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 ...

which is used as a 7-day long-acting

injection Injection or injected may refer to: Science and technology * Injective function, a mathematical function mapping distinct arguments to distinct values * Injection (medicine), insertion of liquid into the body with a syringe * Injection, in broadca ...

in the treatment of moderate to severe

postoperative 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, ...

. The compound is a

diester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are ...

nalbuphine Nalbuphine, sold under the brand names Nubain among others, is an opioid analgesic which is used in the treatment of pain. It is given by injection into a vein, muscle, or fat. Side effects of nalbuphine include sedation, sweatiness, clammin ...

(Nubain) joined via a sebacic acid linker, and acts as a long-lasting

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

of nalbuphine via slow

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

. It was developed to extend the

duration of action Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for ...

of nalbuphine, which has a short duration and requires frequent injections. Whereas nalbuphine must be injected every 4 to 6 hours, a single injection of DNS lasts for up to 7 to 10 days. It was invented by professor Oliver Yoa-Pu Hu (National Defense Medical Center) and codeveloped with Lumosa Therapeutics. Naldebain received market approvals from Taiwan FDA in March 2017,

Health Sciences Authority The Health Sciences Authority (HSA) is a statutory board under the Ministry of Health of the Government of Singapore. It is a multi-disciplinary agency, responsible for applying medical, pharmaceutical and scientific expertise to protect and ...

Singapore Singapore (), officially the Republic of Singapore, is a sovereign island country and city-state in maritime Southeast Asia. It lies about one degree of latitude () north of the equator, off the southern tip of the Malay Peninsula, borde ...

in December 2020, the Ministry of Public Health of Thailand in December 2021, the Drug Control Authority of Malaysia in 2022, State Service of Ukraine on Medicines and Drugs Control and Brunei Darussalam Medicines Control Authority (BDMCA) in 2023. Development is ongoing 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 ...

, China, Korea, and the Philippines.

Medical uses

Naldebain is indicated for the relief of moderate to severe acute postsurgical pain, administered intramuscularly. The product is available in single-use vials; 2 mL single use vial (75 mg/mL) for IM injection is packaged in a carton. Naldebain Eng Pack

Pharmacology

Pharmacodynamics

Nalbuphine, and hence DNS, acts as a mixed agonist/antagonist

opioid modulator An opioid modulator (or opioid receptor modulator) is a drug which has mixed agonist and antagonist actions at different opioid receptors and thus cannot clearly be described as either an opioid ''agonist'' or ''antagonist''. An example of an opioi ...

, or more specifically as a moderate-

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versu ...

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 ...

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

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 � ...

and as a high-

of the

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 ...

Pharmacokinetics

The release mechanism of dinalbuphine sebacate (DNS) upon IM injection is as follows: # Upon intramuscular injection, Naldebain first forms an oil

depot Depot ( or ) may refer to: Places * Depot, Poland, a village * Depot Island, Kemp Land, Antarctica * Depot Island, Victoria Land, Antarctica * Depot Island Formation, Greenland Brands and enterprises * Maxwell Street Depot, a restaurant in ...

in the muscle # The oil depot gradually disperses as small droplets in the surrounding tissues # The prodrug dinalbuphine sebacate gradually diffuses out from the droplets, after which it gets

hydrolyzed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

to the active ingredient nalbuphine via two different mechanisms: #* a small portion of the prodrug gets hydrolyzed by esterases to release the active ingredient, nalbuphine, in the surrounding tissue cells #* the majority of the prodrug enters the bloodstream through local tissue lymph drainage and gets hydrolyzed to nalbuphine in the blood

References

External links

Naldebain information - Lumosa Therapeutics website
{{Opioid receptor modulators Analgesics Cyclobutyl compounds 4,5-Epoxymorphinans Ethers Kappa-opioid receptor agonists Mu-opioid receptor agonists Mu-opioid receptor antagonists Phenols Semisynthetic opioids Tertiary alcohols