Naltalimide (
INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
) (code name TRK-130, formerly TAK 363) is a novel,
centrally-acting
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 use ...
drug which is under development by
and
Toray
is a multinational corporation headquartered in Japan that specializes in industrial products centered on technologies in organic synthetic chemistry, polymer chemistry, and biochemistry.
Its founding business areas were fibers and textiles, ...
for the treatment of
overactive bladder
Overactive bladder (OAB) is a condition where there is a frequent feeling of needing to urinate to a degree that it negatively affects a person's life. The frequent need to urinate may occur during the day, at night, or both. If there is loss ...
/
urinary incontinence
Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geri ...
.
It acts as a potent and selective
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 antagonis ...
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 Π...
(K
i = 0.268 nM,
EC50 = 2.39 nM,
Emax = 66.1%) over the
δ-opioid (K
i = 121 nM,
EC50 = 26.1 nM,
Emax = 71.0%) 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 ...
s (K
i = 8.97 nM,
EC50 = 9.51 nM,
Emax = 62.6%).
Notably, naltalimide somehow appears to lack certain undesirable
side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s such as
constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
seen with other μ-opioid receptor agonists such as
morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...
.
It enhances
bladder
The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...
storage via suppression of the afferent limb of the
micturition
Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...
reflex pathway.
References
4,5-Epoxymorphinans
Mu-opioid receptor agonists
Phthalimides
Takeda Pharmaceutical Company brands
{{nervous-system-drug-stub
Toray Industries