Tipepidine

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.[1][5]

Tipepidine
Clinical data
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
Identifiers
  • 3-(di-2-thienylmethylene)-1-methylpiperidine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC15H17NS2
Molar mass275.43 g·mol−1
3D model (JSmol)
  • s1cccc1/C(c2sccc2)=C3\CCCN(C)C3
  • InChI=1S/C15H17NS2/c1-16-8-2-5-12(11-16)15(13-6-3-9-17-13)14-7-4-10-18-14/h3-4,6-7,9-10H,2,5,8,11H2,1H3 checkY
  • Key:JWIXXNLOKOAAQT-UHFFFAOYSA-N checkY
  (verify)

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.[5]

Tipepidine has been investigated as a potential psychiatric drug. It is being investigated in depression,[3][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

References
  1. Ganellin CR, Triggle DJ (21 November 1996). Dictionary of Pharmacological Agents. CRC Press. pp. 1988–. ISBN 978-0-412-46630-4.
  2. Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 1649–. ISBN 978-3-88763-075-1.
  3. Kawaura K, Ogata Y, Inoue M, Honda S, Soeda F, Shirasaki T, Takahama K (December 2009). "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. doi:10.1016/j.bbr.2009.07.004. PMID 19616036. S2CID 29236491.
  4. ES 272195, "Procedure for the preparation of a new piperidine derivative of anti-nutritional activity", published 1 March 1962, assigned to Antonio Gallardo SA.
  5. Imai Y, Ishii W, Endo A, Arakawa C, Kohira R, Fujita Y, et al. (October 2011). "Tipepidine hibenzate intoxication". Pediatrics International. 53 (5): 779–781. doi:10.1111/j.1442-200X.2010.03297.x. PMID 21955016. S2CID 205484528.
  6. Kawaura K, Honda S, Soeda F, Shirasaki T, Takahama K (May 2010). "[Novel antidepressant-like action of drugs possessing GIRK channel blocking action in rats]". Yakugaku Zasshi. 130 (5): 699–705. doi:10.1248/yakushi.130.699. PMID 20460867.
  7. Sasaki T, Hashimoto K, Tachibana M, Kurata T, Kimura H, Komatsu H, et al. (2014). "Tipepidine in adolescent patients with depression: a 4 week, open-label, preliminary study". Neuropsychiatric Disease and Treatment. 10: 719–722. doi:10.2147/NDT.S63075. PMC 4015794. PMID 24833905.
  8. Honda S, Kawaura K, Soeda F, Shirasaki T, Takahama K (January 2011). "The potent inhibitory effect of tipepidine on marble-burying behavior in mice". Behavioural Brain Research. 216 (1): 308–312. doi:10.1016/j.bbr.2010.08.010. PMID 20713091. S2CID 21118027.
  9. Sasaki T, Hashimoto K, Tachibana M, Kurata T, Okawada K, Ishikawa M, et al. (2014). "Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study". Neuropsychiatric Disease and Treatment. 10: 147–151. doi:10.2147/NDT.S58480. PMC 3908907. PMID 24493927.
  10. Hashimoto K, Sasaki T (February 2015). "Old drug tipepidine as new hope for children with ADHD". The Australian and New Zealand Journal of Psychiatry. 49 (2): 181–182. doi:10.1177/0004867414553952. PMID 25280911. S2CID 8496750.
  11. Dehbozorghi S, Bagheri S, Moradi K, Shokraee K, Mohammadi MR, Akhondzadeh S (November 2019). "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. doi:10.1111/pcn.12913. PMID 31294924. S2CID 195879810.
  12. Hamasaki R, Shirasaki T, Soeda F, Takahama K (November 2013). "Tipepidine activates VTA dopamine neuron via inhibiting dopamine D₂ receptor-mediated inward rectifying K⁺ current". Neuroscience. 252: 24–34. doi:10.1016/j.neuroscience.2013.07.044. PMID 23896570. S2CID 207253362.
  13. Hamao K, Kawaura K, Soeda F, Hamasaki R, Shirasaki T, Takahama K (May 2015). "Tipepidine increases dopamine level in the nucleus accumbens without methamphetamine-like behavioral sensitization". Behavioural Brain Research. 284: 118–124. doi:10.1016/j.bbr.2015.02.012. PMID 25687844. S2CID 22324207.
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