Tipepidine Explained

Tipepidine (INN) (brand names Asverin, Antupex, Asvelik, Asvex, Bitiodin, Cofdenin A, Hustel, Nodal, Sotal), also known as tipepidine hibenzate (JAN), is a synthetic, non-opioid antitussive and expectorant of the thiambutene class.^{[1] [2]} It acts as an inhibitor of G protein-coupled inwardly-rectifying potassium channels (GIRKs).^[3] The drug was discovered in the 1950s,^[4] and was developed in Japan in 1959.^[5] It is used as the hibenzate and citrate salts.

The usual dose is 20 mg every 4 - 6 hours. Possible side effects of tipepidine, especially in overdose, may include drowsiness, vertigo, delirium, disorientation, loss of consciousness, and confusion.

Tipepidine has been investigated as a potential psychiatric drug. It is being investigated in depression,^{[6] [7]} obsessive-compulsive disorder,^[8] and attention-deficit hyperactivity disorder (ADHD).^{[9] [10] [11]} Through inhibition of GIRK channels, tipepidine increases dopamine levels in the nucleus accumbens, but without increasing locomotor activity or producing methamphetamine-like behavioral sensitization, and this action appears to be at least partly responsible for its antidepressant-like effects in rodents.^{[12] [13]}

See also

• Cough syrup
• Noscapine
• Codeine; Pholcodine
• Dextromethorphan; Dimemorfan
• Racemorphan; Dextrorphan; Levorphanol
• Butamirate
• Pentoxyverine
• Cloperastine; Levocloperastine
• Guaifenesin
• Timepidium bromide

Notes and References

1. Book: Ganellin CR, Triggle DJ . Dictionary of Pharmacological Agents. 21 November 1996. CRC Press. 978-0-412-46630-4. 1988–.
2. Book: Index Nominum 2000: International Drug Directory. January 2000. Taylor & Francis. 978-3-88763-075-1. 1649–.
3. Kawaura K, Ogata Y, Inoue M, Honda S, Soeda F, Shirasaki T, Takahama K . The centrally acting non-narcotic antitussive tipepidine produces antidepressant-like effect in the forced swimming test in rats . Behavioural Brain Research . 205 . 1 . 315–318 . December 2009 . 19616036 . 10.1016/j.bbr.2009.07.004 . 29236491 .
4. ES . 272195 . Procedure for the preparation of a new piperidine derivative of anti-nutritional activity . 1 March 1962 . Antonio Gallardo SA . . .
5. Imai Y, Ishii W, Endo A, Arakawa C, Kohira R, Fujita Y, Fuchigami T, Mugishima H . 6 . Tipepidine hibenzate intoxication . Pediatrics International . 53 . 5 . 779–781 . October 2011 . 21955016 . 10.1111/j.1442-200X.2010.03297.x . 205484528 .
6. Kawaura K, Honda S, Soeda F, Shirasaki T, Takahama K . [Novel antidepressant-like action of drugs possessing GIRK channel blocking action in rats] . Yakugaku Zasshi . 130 . 5 . 699–705 . May 2010 . 20460867 . 10.1248/yakushi.130.699 . free .
7. Sasaki T, Hashimoto K, Tachibana M, Kurata T, Kimura H, Komatsu H, Ishikawa M, Hasegawa T, Shiina A, Hashimoto T, Kanahara N, Shiraishi T, Iyo M . 6 . Tipepidine in adolescent patients with depression: a 4 week, open-label, preliminary study . Neuropsychiatric Disease and Treatment . 10 . 719–722 . 2014 . 24833905 . 4015794 . 10.2147/NDT.S63075 . free .
8. Honda S, Kawaura K, Soeda F, Shirasaki T, Takahama K . The potent inhibitory effect of tipepidine on marble-burying behavior in mice . Behavioural Brain Research . 216 . 1 . 308–312 . January 2011 . 20713091 . 10.1016/j.bbr.2010.08.010 . 21118027 .
9. Sasaki T, Hashimoto K, Tachibana M, Kurata T, Okawada K, Ishikawa M, Kimura H, Komatsu H, Ishikawa M, Hasegawa T, Shiina A, Hashimoto T, Kanahara N, Shiraishi T, Iyo M . 6 . Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study . Neuropsychiatric Disease and Treatment . 10 . 147–151 . 2014 . 24493927 . 3908907 . 10.2147/NDT.S58480 . free .
10. Hashimoto K, Sasaki T . Old drug tipepidine as new hope for children with ADHD . The Australian and New Zealand Journal of Psychiatry . 49 . 2 . 181–182 . February 2015 . 25280911 . 10.1177/0004867414553952 . 8496750 .
11. Dehbozorghi S, Bagheri S, Moradi K, Shokraee K, Mohammadi MR, Akhondzadeh S . Efficacy and safety of tipepidine as adjunctive therapy in children with attention-deficit/hyperactivity disorder: Randomized, double-blind, placebo-controlled clinical trial . Psychiatry and Clinical Neurosciences . 73 . 11 . 690–696 . November 2019 . 31294924 . 10.1111/pcn.12913 . 195879810 . free .
12. Hamasaki R, Shirasaki T, Soeda F, Takahama K . Tipepidine activates VTA dopamine neuron via inhibiting dopamine D₂ receptor-mediated inward rectifying K⁺ current . Neuroscience . 252 . 24–34 . November 2013 . 23896570 . 10.1016/j.neuroscience.2013.07.044 . 207253362 .
13. Hamao K, Kawaura K, Soeda F, Hamasaki R, Shirasaki T, Takahama K . Tipepidine increases dopamine level in the nucleus accumbens without methamphetamine-like behavioral sensitization . Behavioural Brain Research . 284 . 118–124 . May 2015 . 25687844 . 10.1016/j.bbr.2015.02.012 . 22324207 .