FAAH enzyme: nootropics and compounds | sci-wiki

BIA 10-2474

BIA 10-2474 is an investigational, orally active fatty acid amide hydrolase (FAAH) inhibitor developed by the Portuguese pharmaceutical company Bial as a candidate treatment for chronic pain, anxiety, and mood disorders. By blocking FAAH, the enzyme that degrades the endocannabinoid anandamide, it was intended to raise endocannabinoid tone and produce analgesic and anxiolytic effects. In January 2016 a Phase 1 healthy-volunteer trial in Rennes, France produced an unanticipated, rapidly progressive neurologic syndrome in the high repeated-dose cohort: one volunteer died and several others were hospitalized with symmetric brain lesions. Development was halted, and subsequent proteomic work showed the compound is a promiscuous inhibitor of multiple lipases and off-target enzymes rather than a selective FAAH blocker. It is now regarded as a landmark case study in drug-safety science and is not available or used outside that historical and investigational context.

reference

Cannabinoid

OL-135

OL-135 is a reversible, competitive fatty acid amide hydrolase (FAAH) inhibitor of the alpha-ketoheterocycle class, developed by the Boger laboratory at The Scripps Research Institute as a chemical tool to raise endogenous anandamide. Built around an electrophilic alpha-ketooxazole warhead (a pyridyl-activated ketone), it inhibits FAAH in the low-nanomolar range and is selective over other serine hydrolases. Unlike the irreversible carbamate inhibitor URB597, OL-135 binds the enzyme reversibly, forming a deprotonated hemiketal with the catalytic serine that mimics the tetrahedral reaction intermediate. In rodent studies it elevates brain anandamide and produces cannabinoid-receptor-mediated analgesia, anti-allodynia, anti-pruritic and anti-inflammatory effects without the overt psychoactivity of direct CB1 agonists. OL-135 remains an investigational research compound; it never advanced to human clinical trials, but it served as the lead scaffold for a large family of orally active, long-acting FAAH inhibitors.

reference

Cannabinoid

URB597

URB597, also known as KDS-4103, is a potent and selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme that breaks down the endocannabinoid anandamide. By blocking FAAH, URB597 raises anandamide levels and amplifies endocannabinoid signaling, producing anxiolytic, antidepressant-like, and analgesic effects in animal models without the full intoxicating profile of direct cannabinoid agonists [1][2][3]. It is one of the most extensively used FAAH inhibitor research tools.

reference