Chemistry:Iproheptine

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Iproheptine, also known as N-isopropyl-1,5-dimethylhexylamine or N-isopropyloctodrine and sold under the brand names Metron and Susat, is a nasal decongestant which has been marketed in Japan.[1][2][3] It is described as a vasoconstrictor and antihistamine.[1][2][3] The drug is available over-the-counter in Japan.[4]

Pharmacology

Pharmacodynamics

Iproheptine is described as a decongestant, vasoconstrictor, and antihistamine.[1][2][3] Its pharmacology was characterized in a series of several preclinical studies published in the 1960s.[5][6][7][8][9][10]

The drug was found to have anticholinergic- and antihistamine-like effects that were described as more potent than those of ephedrine.[6][8][10] It was said to have hypotensive and cardiac inhibitive actions that made it differ from other known alkylamine and arylalkylamine sympathomimetics.[6][8] The effects of iproheptine on blood vessels, pupils, and saliva secretion were all said to be very weak.[6] It produced bronchodilation, vasoconstriction, and hemostasis similarly to ephedrine or methoxyphenamine.[7][10] Iproheptine showed no effect against hexobarbital-induced sleep.[7] Conversely, it showed an antidepressant- or stimulant-like effect in the forced swim test (FST).[9]

Close analogues of iproheptine, such as methylhexanamine and tuaminoheptane, are known to act as norepinephrine and/or dopamine releasing agents by interacting with the monoamine transporters, and this is thought to underlie their sympathomimetic and stimulant effects.[11][12][13][14][15][16]

Pharmacokinetics

In contrast to arylalkylamines like phenethylamines and tryptamines, iproheptine is not metabolized by monoamine oxidase (MAO).[9]

Chemistry

Iproheptine, also known as N-isopropyl-1,5-dimethylhexylamine or as N-isopropyloctodrine, is an alkylamine and the N-isopropyl derivative of octodrine (2-amino-6-methylheptane or 1,5-dimethylhexylamine (1,5-DMHA)).[1][2][3]

Aside from octodrine, it is also closely structurally related to other alkylamines, including 1,3-dimethylbutylamine (1,3-DMBA), 1,4-dimethylamylamine (1,4-DMAA), heptaminol (2-methyl-6-amino-2-heptanol), isometheptene (2-methyl-6-methylamino-2-heptene), methylhexanamine (1,3-dimethylamylamine (1,3-DMAA)), and tuaminoheptane (tuamine; 2-aminoheptane or 1-methylhexylamine).[1][2][3]

Iproheptine shows structural similarity to what would be 3- or 4-methyl-N-isopropylamphetamine, but with the equivalent of the phenyl ring open and incomplete (i.e., missing two carbon atoms, saturated, and the carbons not connected to form a ring).[17][1]

The predicted log P (XLogP3) of iproheptine is 3.6.[17]

History

Iproheptine was first described in the scientific literature by 1960[5][6] and was first patented by 1962.[1] It remained marketed in Japan in 2004.[2]

Society and culture

Names

Iproheptine is the generic name of the drug and its INN.[1][2] In the case of the hydrochloride salt, its generic name is iproheptine hydrochloride and this is its JAN.[2] The drug is marketed under the brand names Metron and Susat (both as the hydrochloride salt).[1][2]

Availability

Iproheptine appears to have been marketed only in Japan.[2] It is available over-the-counter in this country.[4]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. 2014. p. 802. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA802. Retrieved 30 August 2024. 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 Schweizerischer Apotheker-Verein (2004). Index Nominum: International Drug Directory. Medpharm Scientific Publishers. p. 656. ISBN 978-3-88763-101-7. https://books.google.com/books?id=EgeuA47Ocm4C&pg=PA656. Retrieved 30 August 2024. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Drugs: Synonyms and Properties. Routledge Revivals. Taylor & Francis. 2018. p. 286. ISBN 978-1-351-78990-5. https://books.google.com/books?id=dloPEAAAQBAJ&pg=PA286. Retrieved 30 August 2024. "Iproheptine 13946-02-6 6243 CHAN N-Isopropyl-1,5-dimethylhexylamine. Metron; Metron S. Antihistaminic." 
  4. ↑ 4.0 4.1 "KEGG DRUG: Iproheptine Hydrochloride". https://www.genome.jp/dbget-bin/www_bget?drug:D01515. 
  5. ↑ 5.0 5.1 "Pharmacological Studies on Alkylaminoheptane Derivatives. I: Tracheal Muscle Spasmolytic Action of N-Alkyl-1, 5-dimethylhexylamine Derivatives". Yakugaku Zasshi 80 (9): 1153–1155. 1960. doi:10.1248/yakushi1947.80.9_1153. ISSN 0031-6903. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 "Pharmacological Studies on Alkylaminoheptane Derivatives. II: Pharmacological Action of N-Isopropyl-1, 5-dimethylhexylamine Hydrochloride. (1)". Yakugaku Zasshi 80 (9): 1156–1159. 1960. doi:10.1248/yakushi1947.80.9_1156. ISSN 0031-6903. 
  7. ↑ 7.0 7.1 7.2 "Pharmacological Studies on Alkylaminoheptane Derivatives. III: Pharmacological Action of N-Isopropyl-1, 5-dimethylhexylamine Hydrochloride. (2)". Yakugaku Zasshi 81 (3): 394–402. 1961. doi:10.1248/yakushi1947.81.3_394. ISSN 0031-6903. 
  8. ↑ 8.0 8.1 8.2 "Pharmacological Studies on Alkylaminoheptane Derivatives. IV: Blood Pressor, Antispasmodic and Capillary Permeability Inhibiting Action of N-Alkyl-1, 5-dimethylhexylamine Derivatives". Yakugaku Zasshi 81 (3): 403–407. 1961. doi:10.1248/yakushi1947.81.3_403. ISSN 0031-6903. 
  9. ↑ 9.0 9.1 9.2 "Pharmacological Studies on Alkylaminoheptane Derivatives. V: Pharmacological Action of N-isopropyl-1, 5-dimethylhexylamine Hydrochloride. (3)". Yakugaku Zasshi 81 (3): 407–414. 1961. doi:10.1248/yakushi1947.81.3_407. ISSN 0031-6903. 
  10. ↑ 10.0 10.1 10.2 "Pharmacological Studies on Alkylaminoheptane Derivatives. VI: Pharmacological Action of N-Isopropyl-1, 5-dimethyl-hexylamine Hydrochloride. (4)". Yakugaku Zasshi 81 (3): 415–420. 1961. doi:10.1248/yakushi1947.81.3_415. ISSN 0031-6903. 
  11. ↑ "The Alkylamine Stimulant 1,3-Dimethylamylamine Exhibits Substrate-Like Regulation of Dopamine Transporter Function and Localization". J Pharmacol Exp Ther 386 (2): 266–273. August 2023. doi:10.1124/jpet.122.001573. PMID 37348963. 
  12. ↑ "Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA)". Br J Pharmacol 154 (3): 606–622. June 2008. doi:10.1038/bjp.2008.124. PMID 18500382. 
  13. ↑ "Effect of tuamine, heptaminol and two analogues on uptake and release of catecholamines in cultured chromaffin cells". Biochem Pharmacol 40 (4): 821–825. August 1990. doi:10.1016/0006-2952(90)90322-c. PMID 2386550. 
  14. ↑ "Methylhexaneamine causes tachycardia and pressor responses indirectly by releasing noradrenaline in the rat". Eur J Pharmacol 843: 121–125. January 2019. doi:10.1016/j.ejphar.2018.10.047. PMID 30395850. 
  15. ↑ "Structure-based discovery of prescription drugs that interact with the norepinephrine transporter, NET". Proc Natl Acad Sci U S A 108 (38): 15810–15815. September 2011. doi:10.1073/pnas.1106030108. PMID 21885739. Bibcode: 2011PNAS..10815810S. 
  16. ↑ "Pharmacological profiles of compounds in preworkout supplements ("boosters")". Eur J Pharmacol 859. September 2019. doi:10.1016/j.ejphar.2019.172515. PMID 31265842. 
  17. ↑ 17.0 17.1 "Iproheptine". https://pubchem.ncbi.nlm.nih.gov/compound/19917. 



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