TAK-137 / Takeda - LARVOL DELTA

Electrophysiological characterization of a novel AMPA receptor potentiator, TAK-137, in rat hippocampal neurons. (PubMed, Neurosci Lett) - "These results indicate that TAK-137 is a highly potent and selective potentiator with little agonistic effect against native AMPA-Rs. Much greater agonistic effects of LY451646 than of TAK-137 may contribute to the increased risks of seizure and bell-shaped dose response in vivo."

Journal • Preclinical • CNS Disorders • Epilepsy

Safety, Tolerability, and Pharmacokinetics of Multiple Rising Doses of TAK-137 in Adults With Attention-Deficit/Hyperactivity Disorder (clinicaltrials.gov) - P1; N=50; Not yet recruiting; Sponsor: Takeda

New P1 trial • Biosimilar • Myositis

TAK-137, an AMPA receptor potentiator with little agonistic effect, produces antidepressant-like effect without causing psychotomimetic effects in rats. (PubMed, Pharmacol Biochem Behav) - "Ketamine induced hyperlocomotion and PPI reduction, which may be associated with psychotomimetic effects, while TAK-137 did not. TAK-137 may be a safer and rapid-onset therapeutic drug for the treatment of major depressive disorder, including TRD."

Journal • Preclinical

Preclinical characterization of AMPA receptor potentiator TAK-137 as a therapeutic drug for schizophrenia. (PubMed, Pharmacol Res Perspect) - "At 10 mg kg p.o., TAK-137 partially inhibited methamphetamine-induced hyperlocomotion in rats, and at 3, 10, and 30 mg kg p.o., TAK-137 partially inhibited MK-801-induced hyperlocomotion in mice, suggesting weak effects on the positive symptoms of schizophrenia...TAK-137 enhanced attention in the five-choice serial reaction time task in rats at 0.2 mg kg p.o., and improved working memory both in rats and monkeys: 0.2 and 0.6 mg kg p.o. ameliorated MK-801-induced deficits in the radial arm maze test in rats, and 0.1 mg kg p.o. improved the performance of ketamine-treated monkeys in the delayed matching-to-sample task. At 0.1 and 1 mg kg p.o., TAK-137 improved the cognitive flexibility of subchronic phencyclidine-treated rats in the reversal learning test. Thus, TAK-137-type AMPA receptor potentiators with low intrinsic activity may offer new therapies for schizophrenia."

Journal • Preclinical

TAK-137, an AMPA-R potentiator with little agonistic effect, has a wide therapeutic window. (PubMed, Neuropsychopharmacology) - "Thus, TAK-137 is a promising AMPA-R potentiator with potent procognitive effects and lower risks of bell-shaped response and seizure. These data may open the door for the development of AMPA-R potentiators as therapeutic drugs for psychiatric and neurological diseases."

Journal

Characterization of the AMPA Receptor Potentiators With Little Agonistic Effects TAK-137/TAK-653 as Potential Antidepressants (ASCP 2019) - "Individual Abstract Purpose The N-methyl-D-aspartate receptor antagonist ketamine has rapid-onset and sustained antidepressant activity in patients with treatment-resistant depression (TRD). TAK-653 has been selected as an investigational agent. Learning Objectives Describe a novel strategy for discovering AMPA receptor (AMPA-R) potentiators with lower risks of bell-shaped response and a wider safety margin against seizure [1, 2] Review the antidepressant-like effect and psychotomimetic activity of TAK-137 and TAK-653, the AMPA-R potentiators with little agonistic effect"