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 via inhibition of GIRK channels, but without increasing motor activity or producing methamphetamine-like behavioral 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 symptomatology.2
A placebo-based double-blind study found a beneficial 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
Hashimoto, Sasaki (2015): Old drug tipepidine as new hope for children with ADHD. Aust N Z J Psychiatry. 2015 Feb;49(2):181-2. doi: 10.1177/0004867414553952. ↥
Sasaki, Hashimoto, Tachibana, Kurata, Okawada, Ishikawa, Kimura, Komatsu, Ishikawa, Hasegawa, Shiina, Hashimoto, Kanahara, Shiraishi, Iyo (2014): Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study. Neuropsychiatr Dis Treat. 2014 Jan 24;10:147-51. doi: 10.2147/NDT.S58480. eCollection 2014. ↥
Dehbozorghi, Bagheri, Moradi, Shokraee, Mohammadi, Akhondzadeh (2019): Efficacy and safety of tipepidine as adjunctive therapy in children with attention-deficit/hyperactivity disorder: Randomized, double-blind, placebo-controlled clinical trial. Psychiatry Clin Neurosci. 2019 Nov;73(11):690-696. doi: 10.1111/pcn.12913. PMID: 31294924. n = 53 ↥
Pozzi M, Bertella S, Gatti E, Peeters GGAM, Carnovale C, Zambrano S, Nobile M (2020): Emerging drugs for the treatment of attention-deficit hyperactivity disorder (ADHD). Expert Opin Emerg Drugs. 2020 Dec;25(4):395-407. doi: 10.1080/14728214.2020.1820481. PMID: 32938246. ↥
Nazarova VA, Sokolov AV, Chubarev VN, Tarasov VV, Schiöth HB (2022): Treatment of ADHD: Drugs, psychological therapies, devices, complementary and alternative methods as well as the trends in clinical trials. Front Pharmacol. 2022 Nov 17;13:1066988. doi: 10.3389/fphar.2022.1066988. PMID: 36467081; PMCID: PMC9713849. ↥