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Tipepidine for ADHD


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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Sawamoto A, Okada M, Matsuoka N, Okuyama S, Nakajima M (2024): Tipepidine activates AMPK and improves adipose tissue fibrosis and glucose intolerance in high-fat diet-induced obese mice. FASEB J. 2024 Mar 15;38(5):e23542. doi: 10.1096/fj.202301861RR. PMID: 38466234.

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