Cloperastine Explained

Cloperastine (INN) or cloperastin, in the forms of cloperastine hydrochloride (JAN) (brand names Hustazol, Nitossil, Seki) and cloperastine fendizoate, is an antitussive and antihistamine that is marketed as a cough suppressant in Japan, Hong Kong, and in some European countries.^{[1] [2] [3]} It was first introduced in 1972 in Japan, and then in Italy in 1981.^[4]

Side effects

Adverse effects may include sedation, drowsiness, heartburn, and thickening of bronchial secretions.^[5]

Pharmacology

The precise mechanism of action of cloperastine is not fully clear, but several different biological activities have been identified for the drug, of which include: ligand of the σ₁ receptor (K_i = 20 nM) (likely an agonist),^[6] GIRK channel blocker (described as "potent"),^{[7] [8] [9] [10]} antihistamine (K_i = 3.8 nM for the H₁ receptor), and anticholinergic.^[11] It is thought that the latter two properties contribute to side effects, such as sedation and somnolence, while the former two may be involved in or responsible for the antitussive efficacy of cloperastine.

Synthesis

The halogenation of 4-Chlorobenzhydrol [119-56-2] (1) with phosphorus tribromide in tetrachloromethane gives 1-(Bromophenylmethyl)-4-chlorobenzene [948-54-9] (2). Treatment with ethylenechlorohydrin (2-Chloroethanol) [107-07-3] (3) gives 1-(4-Chlorobenzhydryl)oxy-2-chloroethane [5321-46-0] (4). Reaction with piperidine (5) completes the synthesis of Cloperastine (6).

See also

• Cough syrup
• Noscapine
• Codeine; Pholcodine
• Dextromethorphan; Dimemorfan
• Racemorphan; Dextrorphan; Levorphanol
• Butamirate
• Pentoxyverine
• Tipepidine
• Levocloperastine

Notes and References

1. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies . 14 November 2014 . Springer. 301– . 978-1-4757-2085-3 .
2. Book: Swiss Pharmaceutial Society . Index Nominum 2000: International Drug Directory . January 2000 . Taylor & Francis . 978-3-88763-075-1 . 261– .
3. Catania MA, Cuzzocrea S . Pharmacological and clinical overview of cloperastine in treatment of cough . Therapeutics and Clinical Risk Management . 7 . 83–92 . 2011 . 21445282 . 3061847 . 10.2147/TCRM.S16643 . free .
4. Book: William Andrew Publishing . Pharmaceutical Manufacturing Encyclopedia . 22 October 2013 . Elsevier . 978-0-8155-1856-3 . 1103– .
5. Book: 0-8103-7177-4 . Drugs Available Abroad, 1st Edition . 29 . 1991 . Schlesser JL . Derwent Publications Ltd..
6. Gregori-Puigjané E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, Marnett L, Roth BL, Shoichet BK . 6 . Identifying mechanism-of-action targets for drugs and probes . Proceedings of the National Academy of Sciences of the United States of America . 109 . 28 . 11178–83 . July 2012 . 22711801 . 3396511 . 10.1073/pnas.1204524109 . 2012PNAS..10911178G . free .
7. Book: Chung KF, Widdicombe J . Pharmacology and Therapeutics of Cough . 30 September 2008 . Springer Science & Business Media. 230– . 9783540798422 .
8. Soeda F, Fujieda Y, Kinoshita M, Shirasaki T, Takahama K . Centrally acting non-narcotic antitussives prevent hyperactivity in mice: Involvement of GIRK channels . Pharmacology, Biochemistry, and Behavior . 144 . 26–32 . May 2016 . 26892760 . 10.1016/j.pbb.2016.02.006 . 978-3-540-79842-2 . 30118634 . 612742272 .
9. Yamamoto G, Soeda F, Shirasaki T, Takahama K . [Is the GIRK channel a possible target in the development of a novel therapeutic drug of urinary disturbance?] . Yakugaku Zasshi . 131 . 4 . 523–32 . April 2011 . 21467791 . 10.1248/yakushi.131.523 . free .
10. 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 .
11. Book: Korolkovas A . Essentials of Medicinal Chemistry . 16 August 1988 . Wiley . 978-0-471-88356-2 .