Tipepidine for ADHD

Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine) is a synthetic, non-opioid cough blocker (antitussive). Tipepidine increases dopamine levels in the nucleus accumbens by inhibiting GIRK channels, but without increasing motor activity or producing methamphetamine-like behavioural sensitization.
It has been used in Japan since 1959 and could be an interesting alternative to MPH and AMP due to its lack of stimulant properties.¹

Tipepidine alone shows significant improvements in ADHD symptoms.²
A placebo-based double-blind study found a positive effect of tipepidine given in addition to MPH.³

Tipepidine showed some promising results in improving ADHD symptoms in several Phase 2 clinical trials.⁴ Further studies have not yet been initiated.⁵

Tipepidin improves metabolism and activates AMPK.⁶
It reduced high-fat diet-induced weight gain in mice, reduced lipid accumulation in the liver and increased the weight of epididymal white adipose tissue (eWAT) in obese mice (DIO).
Tipepidin inhibited obesity-induced fibrosis in eWAT.
Tipepidine activated AMP-activated protein kinase (AMPK) in eWAT of DIO mice and 3T3-L1 cells, which could be reversed by transfection of liver kinase B1 siRNA into 3T3-L1 cells.