Olorinab (APD371) is a drug being developed by

Arena Pharmaceuticals Arena Pharmaceuticals, Inc. is an American biopharmaceutical company founded in 1997 and headquartered in San Diego, California. The company has small molecule drugs in development for possible clinical utility in multiple therapeutic areas. The ...

for the treatment of gastrointestinal pain associated with

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...

and

irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating, and changes in the consistency of bowel movements. These symptoms may ...

. It acts as a potent and selective

cannabinoid Cannabinoids () are several structural classes of compounds found primarily in the ''Cannabis'' plant or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoact ...

CB₂

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

and is claimed to be orally active and peripherally selective. Initial Phase IIa exploratory

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

s have been successful in patients with quiescent Crohn's disease. Arena initiated the Phase IIb Captivate trial in late July 2019 in patients with

related pain, in constipation and diarrhea predominant sub-types. The Phase IIb trial is expected to enroll 240 participants between the ages of 18 and 70.Three doses of 10 mg, 25 mg, and 50 mg are being tested against

Placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

in a 3:4 prescription ratio with a Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) masking layout. In 2019, a study showed that Olorinab reduces Visceral Hypersensitivity in the TNBS-induced colitis animal model, attempting to control for its

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...

by using a CB2 antagonist (

SR-144,528 SR144528 is a drug that acts as a potent and highly selective CB2 receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Recepto ...

). Results were favorable showing reduced visceral hypersensitivity in animal models of IBD and IBS but not in healthy controls, suggesting that activation of CB2 causes antinociceptive actions in visceral sensory pathways in models of IBD and IBS. Also, SR-144528 prevented olorinab-induced inhibition of colonic nociceptor hypersensitivity, further validating the role of the CB2 receptor in

nociception In physiology, nociception , also nocioception; ) 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 organism to receive a pai ...

References

{{Cannabinoid receptor modulators Cannabinoids Pyrazoles Pyrazines Tert-butyl compounds Carboxamides Peripherally selective drugs Experimental drugs

See also

References