Phenbenzamine Explained

Phenbenzamine, sold under the brand name Antergan and known by the former developmental code name RP-2339, is an antihistamine of the ethylenediamine class which also has anticholinergic properties.^{[1] [2]} It was introduced in 1941 or 1942 and was the first antihistamine to be introduced for medical use.^{[3] [4] [5]} Soon following its introduction, phenbenzamine was replaced by another antihistamine of the same class known as mepyramine (pyrilamine; Neoantergan).^[6] Following this, other antihistamines, such as diphenhydramine, promethazine, and tripelennamine, were developed and introduced.^[7] Owing to their sedative effects, phenbenzamine and promethazine were assessed in the treatment of manic depression in France in the 1940s and were regarded as promising therapies for such purposes. Whereas phenbenzamine was the first clinically useful antihistamine, piperoxan was the first compound with antihistamine properties to be discovered and was synthesized in the early 1930s.

Chemistry

Synthesis

Phenbenzamine can be prepared by the reaction of N-benzylaniline with 2-chloroethyldimethylamine.^{[8] [9]}

Notes and References

1. Encyclopedia: Phenbenzamine . Encyclopædia Britannica .
2. Book: Maxwell RA, Eckhardt SB . 6 December 2012 . Chloropromazine . Drug Discovery: A Casebook and Analysis . Springer Science & Business Media . 113– . 978-1-4612-0469-5 . https://books.google.com/books?id=35TzBwAAQBAJ&pg=PA113.
3. Book: The Bitterest Pills . Moncrieff . Joanna . Chlorpromazine: The First Wonder Drug . 2013 . 20–38 . Palgrave Macmillan UK . 10.1057/9781137277442_2 . 978-1-137-27743-5 .
4. Book: Williams DA, Foye WO, Lemke TL . 2002 . Chapter 29: Estrogen, Progestins, and Androgens . Foye's Principles of Medicinal Chemistry . Lippincott Williams & Wilkins . 799– . 978-0-683-30737-5 . https://books.google.com/books?id=qLJ6Bs1Qml4C&pg=PA799.
5. Book: Welcome MO . 20 June 2018 . Gastrointestinal Physiology: Development, Principles and Mechanisms of Regulation . Springer . 827– . 978-3-319-91056-7 .
6. Book: Cundell DR, Mickle KE . Developing the Perfect Antihistamine for use in Allergic Conditions: A Voyage in H1 Selectivity . Atta-ur-Rahman . 11 July 2018 . Frontiers in Clinical Drug Research - Anti-Allergy Agents . Bentham Science Publishers . 29– . 978-1-68108-337-7 . https://books.google.com/books?id=EIJoDwAAQBAJ&pg=PA29.
7. Book: Landau R, Achilladelis B, Scriabine A . 1999 . Pharmaceutical Innovation: Revolutionizing Human Health . Chemical Heritage Foundation . 230–231 . 978-0-941901-21-5 .
8. US . 2634293 . Process of preparing a monobasic salt of a secondary amine . Kyrides LP, Zienty FB . 7 April 1953 . Monsanto Chemicals .
9. Kaye IA, Parris CL, Weiner N . A Novel N-Alkylation Reaction . Journal of the American Chemical Society . 75 . 3 . 1953 . 744–745 . 10.1021/ja01099a508.